Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy

ABSTRACT

The present invention relates to tetraline and indane derivatives of the formula (I) 
     
       
         
         
             
             
         
       
     
     or a physiologically tolerated salt thereof. 
     The invention relates to pharmaceutical compositions comprising such tetraline and indane derivatives, and the use of such tetraline and indane derivatives for therapeutic purposes. The tetraline and indane derivatives are GlyT1 inhibitors.

CROSS-REFERENCE TO RELATED APPLICATION

This claims priority to U.S. Provisional Patent Application No.61/373,654, filed on Aug. 13, 2010, the contents of which are herebyincorporated by reference.

BACKGROUND OF THE INVENTION

The present invention relates to tetraline and indane derivatives,pharmaceutical compositions comprising such tetraline and indanederivatives, and the use of such tetraline and indane derivatives fortherapeutic purposes. The tetraline and indane derivatives are GlyT1inhibitors.

Dysfunction of glutamatergic pathways has been implicated in a number ofdisease states in the human central nervous system (CNS) including butnot limited to schizophrenia, cognitive deficits, dementia, Parkinsondisease, Alzheimer disease and bipolar disorder. A large number ofstudies in animal models lend support to the NMDA hypofunctionhypothesis of schizophrenia.

NMDA receptor function can be modulated by altering the availability ofthe co-agonist glycine. This approach has the critical advantage ofmaintaining activity-dependent activation of the NMDA receptor becausean increase in the synaptic concentration of glycine will not produce anactivation of NMDA receptors in the absence of glutamate. Since synapticglutamate levels are tightly maintained by high affinity transportmechanisms, an increased activation of the glycine site will onlyenhance the NMDA component of activated synapses.

Two specific glycine transporters, GlyT1 and GlyT2 have been identifiedand shown to belong to the Na/Cl-dependent family of neurotransmittertransporters which includes taurine, gamma-aminobutyric acid (GABA),proline, monoamines and orphan transporters. GlyT1 and GlyT2 have beenisolated from different species and shown to have only 50% identity atthe amino acid level. They also have a different pattern of expressionin mammalian central nervous system, with GlyT2 being expressed inspinal cord, brainstem and cerebellum and GlyT1 present in these regionsas well as forebrain areas such as cortex, hippocampus, septum andthalamus. At the cellular level, GlyT2 has been reported to be expressedby glycinergic nerve endings in rat spinal cord whereas GlyT1 appears tobe preferentially expressed by glial cells. These expression studieshave led to the suggestion that GlyT2 is predominantly responsible forglycine uptake at glycinergic synapses whereas GlyT1 is involved inmonitoring glycine concentration in the vicinity of NMDA receptorexpressing synapses. Recent functional studies in rat have shown thatblockade of GlyT1 with the potent inhibitor(N-[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)propyl])-sarcosine (NFPS)potentiates NMDA receptor activity and NMDA receptor-dependent long-termpotentiation in rat.

Molecular cloning has further revealed the existence of three variantsof GlyT1, termed GlyT-1a, GlyT-1b and GlyT-1c, each of which displays aunique distribution in the brain and peripheral tissues. The variantsarise by differential splicing and exon usage, and differ in theirN-terminal regions.

The physiological effects of GlyT1 in forebrain regions together withclinical reports showing the beneficial effects of GlyT1 inhibitorsarcosine in improving symptoms in schizophrenia patients suggest thatselective GlyT1 inhibitors represent a new class of antipsychotic drugs.

Glycine transporter inhibitors are already known in the art, forexample:

(see also Hashimoto K., Recent Patents on CNS Drug Discovery, 2006, 1,43-53; Harsing L. G. et al., Current Medicinal Chemistry, 2006, 13,1017-1044; Javitt D. C., Molecular Psychiatry (2004) 9, 984-997;Lindsley, C. W. et al., Current Topics in Medicinal Chemistry, 2006, 6,771-785; Lindsley C. W. et al., Current Topics in Medicinal Chemistry,2006, 6, 1883-1896).

It was one object of the present invention to provide further glycinetransporter inhibitors.

SUMMARY OF THE INVENTION

The present invention relates to tetraline and indane derivatives of theformula (I)

-   -   wherein

-   A is a 5- or 6-membered ring;

-   R is R¹—W-A¹-Q-Y-A²-X¹—;

-   R¹ is hydrogen, alkyl, cycloalkylalkyl, halogenated alkyl,    trialkylsilylalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl,    alkylaminoalkyl, dialkylaminoalkyl, alkylcarbonylaminoalkyl,    alkyloxycarbonylaminoalkyl, alkylaminocarbonylaminoalkyl,    dialkylaminocarbonyl-aminoalkyl, alkylsulfonylaminoalkyl,    (optionally substituted arylalkyl)aminoalkyl, optionally substituted    arylalkyl, optionally substituted heterocyclylalkyl, cycloalkyl,    alkylcarbonyl, alkoxycarbonyl, halogenated alkoxycarbonyl,    aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, (halogenated    alkyl)aminocarbonyl, arylaminocarbonyl, alkenyl, alkynyl, optionally    substituted aryl, hydroxy, alkoxy, halogenated alkoxy,    hydroxyalkoxy, alkoxyalkoxy, aminoalkoxy, alkylaminoalkoxy,    dialkylaminoalkoxy, alkylcarbonylaminoalkoxy,    arylcarbonylaminoalkoxy, alkoxycarbonylaminoalkoxy, arylalkoxy,    alkylsulfonylaminoalkoxy, (halogenated alkyl)sulfonylaminoalkoxy,    arylsulfonylaminoalkoxy, (arylalkyl)sulfonylaminoalkoxy,    heterocyclylsulfonylaminoalkoxy, heterocyclylalkoxy, aryloxy,    heterocyclyloxy, alkylthio, halogenated alkylthio, alkylamino,    (halogenated alkyl)amino, dialkylamino, di-(halogenated alkyl)amino,    alkylcarbonylamino, (halogenated alkyl)carbonylamino,    arylcarbonylamino, alkylsulfonylamino, (halogenated    alkyl)sulfonylamino, arylsulfonylamino or optionally substituted    heterocyclyl;

-   W is —NR⁸— or a bond;

-   A¹ is optionally substituted alkylene or a bond;

-   Q is —S(O)₂— or —C(O)—;

-   Y is —NR⁹— or a bond;

-   A² is optionally substituted alkylene, alkylene-CO—, —CO-alkylene,    alkylene-O-alkylene, alkylene-NR¹⁰-alkylene, optionally substituted    alkenylene, optionally substituted alkynylene, optionally    substituted arylene, optionally substituted heteroarylene or a bond;

-   X¹ is —O—, —NR¹¹—, —S—, optionally substituted alkylene, optionally    substituted alkenylen, optionally substituted alkynylene;

-   R² is hydrogen, halogen, alkyl, halogenated alkyl, hydroxyalkyl,    —CN, alkenyl, alkynyl, optionally substituted aryl, hydroxy, alkoxy,    halogenated alkoxy, alkoxycarbonyl, alkenyloxy, arylalkoxy,    alkylcarbonyloxy, alkylthio, alkylsulfinyl, alkylsulfonyl,    aminosulfonyl, amino, alkylamino, alkenylamino, nitro or optionally    substituted heterocyclyl, or two radicals R² together with the ring    atoms of A to which they are bound form a 5- or 6-membered ring;

-   R³ is hydrogen, halogen, alkyl or alkoxy, or two radicals R³    together with the carbon atom to which they are attached form a    carbonyl group;

-   Y¹ is optionally substituted alkylene;

-   R^(4a) is hydrogen, alkyl, cycloalkylalkyl, halogenated alkyl,    hydroxyalkyl, alkoxyalkyl, aminoalkyl, CH₂CN, aralkyl, cycloalkyl,    —CHO, alkylcarbonyl, (halogenated alkyl)carbonyl, arylcarbonyl,    alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, alkenyl,    —C(═NH)NH₂, —C(═NH)NHCN, alkylsulfonyl, arylsulfonyl, amino, —NO or    heterocyclyl; or

-   R^(4a) is optionally substituted alkylene that is bound to a carbon    atom in Y¹;

-   R^(4b) is hydrogen, alkyl, halogenated alkyl, hydroxyalkyl,    alkoxyalkyl, aminoalkyl, CH₂CN, —CHO, alkylcarbonyl, (halogenated    alkyl)carbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl,    alkylaminocarbonyl, alkenyl, —C(═NH)NH₂, —C(═NH)NHCN, alkylsulfonyl,    arylsulfonyl, amino, —NO or heterocyclyl; or

-   R^(4a), R^(4b)    -   together are optionally substituted alkylene, wherein one —CH₂—        of alkylene may be replaced by an oxygen atom or —NR¹⁶;

-   X² is —O—, —NR⁶—, —S—, >CR^(12a)R^(12b) or a bond;

-   X³ is —O—, —S—, >CR^(13a)R^(13b) or a bond;

-   R⁵ is optionally substituted aryl, optionally substituted cycloalkyl    or optionally substituted heterocyclyl;

-   n is 0, 1 or 2;

-   R⁶ is hydrogen or alkyl;

-   R⁷ is hydrogen or alkyl;

-   R⁸ is hydrogen or alkyl;

-   R⁹ is hydrogen, alkyl, cycloalkyl, aminoalkyl, optionally    substituted arylalkyl or heterocyclyl; or

-   R⁹, R¹    -   together are alkylene; or

-   R⁹ is alkylene that is bound to a carbon atom in A² and A² is    alkylene or to a carbon atom in X¹ and X¹ is alkylene;

-   R¹⁰ is hydrogen, alkyl or alkylsulfonyl;

-   R¹¹ is hydrogen or alkyl, or

-   R⁹, R¹¹    -   together are alkylene,

-   R^(12a) is hydrogen, optionally substituted alkyl, alkylaminoalkyl,    dialkylaminoalkyl, heterocyclylalkyl, optionally substituted aryl or    hydroxy;

-   R^(12b) is hydrogen or alkyl, or

-   R^(12a), R^(12b)    -   together are carbonyl or optionally substituted alkylene,        wherein one —CH₂— of alkylene may be replaced by an oxygen atom        or —NR¹⁴—;

-   R^(13a) is hydrogen, optionally substituted alkyl, alkylaminoalkyl,    dialkylaminoalkyl, heterocyclylalkyl, optionally substituted aryl or    hydroxy;

-   R^(13b) is hydrogen or alkyl, or

-   R^(13a), R^(13b)    -   together are carbonyl or optionally substituted alkylene,        wherein one —CH₂— of alkylene may be replaced by an oxygen atom        or —NR¹⁵—;

-   R¹⁴ is hydrogen or alkyl;

-   R¹⁵ is hydrogen or alkyl; and

-   R¹⁶ is hydrogen or alkyl,    or a physiologically tolerated salt thereof.

According to a second aspect, the present invention relates to tetralineand indane derivatives of the formula (I) or a physiologically toleratedsalt thereof, wherein the Y¹ is a bond, R^(4a) is cycloalkyl and A, R¹,W, A¹, Q, Y, A², R², R³, R^(4b), X², X³, R⁵, n are as defined herein,provided that the tetraline and indane derivative is notpropane-1-sulfonic acid(8-benzyl-7-cyclopropylamino-5,6,7,8-tetrahydro-naphthalen-2-ylmethyl)-amideor a physiologically tolerated salt thereof such as the hydrochloride.

-   Thus, the present invention relates to tetraline and indane    derivatives having the formula (Ia)

wherein A, R¹, W, A¹, Q, Y, A², X¹, R², R³, Y¹, R^(4a), R^(4b), X², X³,R⁵, n are as defined herein.

Further, the present invention relates to tetraline and indanederivatives of formula (I) wherein R is —CN, i.e. tetraline and indanederivatives having the formula (Ib)

wherein A, R², R³, Y¹, R^(4a), R^(4b), X², X³, R⁵, n are as definedherein.

Thus, the term tetraline and indane derivative is used herein to denotein particular tetralines (n=1) and fused cyclohexanes (n=1) wherein thebenzene ring is replaced by a 5- or 6-membered heterocyclic ring as wellas homologous bicyclic compounds wherein n is 0 or 2.

Said compounds of formula (I), i.e., the tetraline and indanederivatives of formula (I) and their physiologically tolerated salts,are glycine transporter inhibitors and thus useful as pharmaceuticals.

The present invention thus further relates to the compounds of formula(I) for use in therapy.

The present invention also relates to pharmaceutical compositions whichcomprise a carrier and a compound of formula (I).

In particular, said compounds, i.e., the tetraline and indanederivatives and their physiologically tolerated salts, are inhibitors ofthe glycine transporter GlyT1.

The present invention thus further relates to the compounds of formula(I) for use in inhibiting the glycine transporter.

The present invention also relates to the use of the compounds offormula (I) in the manufacture of a medicament for inhibiting theglycine transporter GlyT1 and corresponding methods of inhibiting theglycine transporter GlyT1.

Glycine transport inhibitors and in particular inhibitors of the glycinetransporter GlyT1 are known to be useful in treating a variety ofneurologic and psychiatric disorders.

The present invention thus further relates to the compounds of formula(I) for use in treating a neurologic or psychiatric disorder.

The present invention further relates to the compounds of formula (I)for use in treating pain.

The present invention also relates to the use of the compounds offormula (I) in the manufacture of a medicament for treating a neurologicor psychiatric disorder and corresponding methods of treating saiddisorders. The present invention also relates to the use of thecompounds of formula (I) in the manufacture of a medicament for treatingpain and corresponding methods of treating pain.

The present invention further relates to tetraline and indanederivatives of formula (II)

wherein L is an amino-protecting group, Y is NR⁹, and A², X¹, R², R³,Y¹, R^(4a), R^(4b), X², X³, R⁵, n and R⁹ are defined as above.

The tetraline and indane derivatives of formula (II) are useful asintermediates in the preparation of GlyT1 inhibitors, in particularthose of formula (I).

DETAILED DESCRIPTION OF THE INVENTION

Provided that the tetraline and indane derivatives of the formula (I) or(II) of a given constitution may exist in different spatialarrangements, for example if they possess one or more centers ofasymmetry, polysubstituted rings or double bonds, or as differenttautomers, it is also possible to use enantiomeric mixtures, inparticular racemates, diastereomeric mixtures and tautomeric mixtures,preferably, however, the respective essentially pure enantiomers,diastereomers and tautomers of the compounds of formula (I) or (II)and/or of their salts.

According to one embodiment, an enantiomer of the compounds of thepresent invention has the following formula:

wherein A, R, R², R³, Y¹, R^(4a), R^(4b), X², X³, R⁵, n are as definedherein.

According to another embodiment, an enantiomer of the compounds of thepresent invention has the following formula:

wherein A, R, R², R³, Y¹, R^(4a), R^(4b), X², X³, R⁵, n are as definedherein.

According to one embodiment, an enantiomer of the compounds of thepresent invention has the following formula:

wherein A, R, R², R³, Y¹, R^(4a), R^(4b), X², X³, R⁵, n are as definedherein.

According to another embodiment, an enantiomer of the compounds of thepresent invention has the following formula:

wherein A, R, R², R³, Y¹, R^(4a), R^(4b), X², X³, R⁵, n are as definedherein.

The physiologically tolerated salts of the tetraline and indanederivatives of the formula (I) or (II) are especially acid additionsalts with physiologically tolerated acids. Examples of suitablephysiologically tolerated organic and inorganic acids are hydrochloricacid, hydrobromic acid, phosphoric acid, sulfuric acid,C₁-C₄-alkylsulfonic acids, such as methanesulfonic acid, cycloaliphaticsulfonic acids, such as S-(+)-10-camphor sulfonic acid, aromaticsulfonic acids, such as benzenesulfonic acid and toluenesulfonic acid,di- and tricarboxylic acids and hydroxycarboxylic acids having 2 to 10carbon atoms, such as oxalic acid, malonic acid, maleic acid, fumaricacid, lactic acid, tartaric acid, citric acid, glycolic acid, adipicacid and benzoic acid. Other utilizable acids are described, e.g., inFortschritte der Arzneimittelforschung [Advances in drug research],Volume 10, pages 224 ff., Birkhä user Verlag, Basel and Stuttgart, 1966.The physiologically tolerated salts of the tetraline and indanederivatives also include salts of a physiologically tolerated anion withtetraline and indane derivatives wherein one or more than one nitrogenatom is quaternized, e.g. with an alkyl residue (e.g. methyl or ethyl).

The present invention moreover relates to compounds of formula (I) or(II) as defined herein, wherein at least one of the atoms has beenreplaced by its stable, non-radioactive isotope (e.g., hydrogen bydeuterium, ¹²C by ¹³C, ¹⁴N by ¹⁵N, ¹⁶O by ¹⁸O) and preferably wherein atleast one hydrogen atom has been replaced by a deuterium atom.

Of course, such compounds contain more of the respective isotope thanthis naturally occurs and thus is anyway present in the compounds (I) or(II).

Stable isotopes (e.g., deuterium, ¹³O, ¹⁵N, ¹⁸O) are nonradioactiveisotopes which contain one or more additional neutron than the normallyabundant isotope of the respective atom. Deuterated compounds have beenused in pharmaceutical research to investigate the in vivo metabolicfate of the compounds by evaluation of the mechanism of action andmetabolic pathway of the non-deuterated parent compound (Blake et al. J.Pharm. Sci. 64, 3, 367-391 (1975)). Such metabolic studies are importantin the design of safe, effective therapeutic drugs, either because thein vivo active compound administered to the patient or because themetabolites produced from the parent compound prove to be toxic orcarcinogenic (Foster et al., Advances in Drug Research Vol. 14, pp.2-36, Academic Press, London, 1985; Kato et al., J. Labelled Comp.Radiopharmaceut., 36(10):927-932 (1995); Kushner et al., Can. J.Physiol. Pharmacol., 77, 79-88 (1999).

Incorporation of a heavy atom particularly substitution of deuterium forhydrogen, can give rise to an isotope effect that could alter thepharmacokinetics of the drug. This effect is usually insignificant ifthe label is placed at a metabolically inert position of the molecule.

Stable isotope labeling of a drug can alter its physico-chemicalproperties such as pKa and lipid solubility. These changes may influencethe fate of the drug at different steps along its passage through thebody. Absorption, distribution, metabolism or excretion can be changed.Absorption and distribution are processes that depend primarily on themolecular size and the lipophilicity of the substance. These effects andalterations can affect the pharmacodynamic response of the drug moleculeif the isotopic substitution affects a region involved in aligand-receptor interaction.

Drug metabolism can give rise to large isotopic effect if the breakingof a chemical bond to a deuterium atom is the rate limiting step in theprocess. While some of the physical properties of a stableisotope-labeled molecule are different from those of the unlabeled one,the chemical and biological properties are the same, with one importantexception: because of the increased mass of the heavy isotope, any bondinvolving the heavy isotope and another atom will be stronger than thesame bond between the light isotope and that atom. In any reaction inwhich the breaking of this bond is the rate limiting step, the reactionwill proceed slower for the molecule with the heavy isotope due to“kinetic isotope effect”. A reaction involving breaking a C-D bond canbe up to 700 percent slower than a similar reaction involving breaking aC—H bond. If the C-D bond is not involved in any of the steps leading tothe metabolite, there may not be any effect to alter the behavior of thedrug. If a deuterium is placed at a site involved in the metabolism of adrug, an isotope effect will be observed only if breaking of the C-Dbond is the rate limiting step. There is evidence to suggest thatwhenever cleavage of an aliphatic C—H bond occurs, usually by oxidationcatalyzed by a mixed-function oxidase, replacement of the hydrogen bydeuterium will lead to observable isotope effect. It is also importantto understand that the incorporation of deuterium at the site ofmetabolism slows its rate to the point where another metabolite producedby attack at a carbon atom not substituted by deuterium becomes themajor pathway a process called “metabolic switching”.

Deuterium tracers, such as deuterium-labeled drugs and doses, in somecases repeatedly, of thousands of milligrams of deuterated water, arealso used in healthy humans of all ages, including neonates and pregnantwomen, without reported incident (e.g. Pons G and Rey E, Pediatrics 1999104: 633; Coward W A et al., Lancet 1979 7: 13; Schwarcz H P, Control.Clin. Trials 1984 5(4 Suppl): 573; Rodewald L E et al., J. Pediatr. 1989114: 885; Butte N F et al. Br. J. Nutr. 1991 65: 3; MacLennan A H et al.Am. J. Obstet. Gynecol. 1981 139: 948). Thus, it is clear that anydeuterium released, for instance, during the metabolism of compounds ofthis invention poses no health risk.

The weight percentage of hydrogen in a mammal (approximately 9%) andnatural abundance of deuterium (approximately 0.015%) indicates that a70 kg human normally contains nearly a gram of deuterium. Furthermore,replacement of up to about 15% of normal hydrogen with deuterium hasbeen effected and maintained for a period of days to weeks in mammals,including rodents and dogs, with minimal observed adverse effects(Czajka D M and Finkel A J, Ann. N.Y. Acad. Sci. 1960 84: 770; Thomson JF, Ann. New York Acad. Sci. 1960 84: 736; Czakja D M et al., Am. J.Physiol. 1961 201: 357). Higher deuterium concentrations, usually inexcess of 20%, can be toxic in animals. However, acute replacement of ashigh as 15%-23% of the hydrogen in humans' fluids with deuterium wasfound not to cause toxicity (Blagojevic N et al. in “Dosimetry &Treatment Planning for Neutron Capture Therapy”, Zamenhof R, Solares Gand Harling 0 Eds. 1994. Advanced Medical Publishing, Madison Wis. pp.125-134; Diabetes Metab. 23: 251 (1997)).

Increasing the amount of deuterium present in a compound above itsnatural abundance is called enrichment or deuterium-enrichment. Examplesof the amount of enrichment include from about 0.5, 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, 54, 58, 63, 67, 71,75, 79, 84, 88, 92, 96, to about 100 mol %.

The hydrogens present on a particular organic compound have differentcapacities for exchange with deuterium. Certain hydrogen atoms areeasily exchangeable under physiological conditions and, if replaced bydeuterium atoms, it is expected that they will readily exchange forprotons after administration to a patient. Certain hydrogen atoms may beexchanged for deuterium atoms by the action of a deuteric acid such asD₂SO₄/D₂O. Alternatively, deuterium atoms may be incorporated in variouscombinations during the synthesis of compounds of the invention. Certainhydrogen atoms are not easily exchangeable for deuterium atoms. However,deuterium atoms at the remaining positions may be incorporated by theuse of deuterated starting materials or intermediates during theconstruction of compounds of the invention.

Deuterated and deuterium-enriched compounds of the invention can beprepared by using known methods described in the literature. Suchmethods can be carried out utilizing corresponding deuterated andoptionally, other isotope-containing reagents and/or intermediates tosynthesize the compounds delineated herein, or invoking standardsynthetic protocols known in the art for introducing isotopic atoms to achemical structure. Relevant procedures and intermediates are disclosed,for instance in Lizondo, J et al., Drugs Fut, 21(11), 1116 (1996);Brickner, S J et al., J Med Chem, 39(3), 673 (1996); Mallesham, B etal., Org Lett, 5(7), 963 (2003); PCT publications WO1997010223,WO2005099353, WO1995007271, WO2006008754; U.S. Pat. Nos. 7,538,189;7,534,814; 7,531,685; 7,528,131; 7,521,421; 7,514,068; 7,511,013; and USPatent Application Publication Nos. 20090137457; 20090131485;20090131363; 20090118238; 20090111840; 20090105338; 20090105307;20090105147; 20090093422; 20090088416; 20090082471, the methods arehereby incorporated by reference.

The organic moieties mentioned in the above definitions of the variablesare—like the term halogen—collective terms for individual listings ofthe individual group members. The prefix C_(n)—C_(m) indicates in eachcase the possible number of carbon atoms in the group.

Unless indicated otherwise, the term “substituted” means that a radicalis substituted with 1, 2 or 3, especially 1, substituent which are inparticular selected from the group consisting of halogen, C₁-C₄-alkyl,hydroxy-C₁-C₄-alkyl, C₃-C₁₂-heterocyclylalkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,amino-C₁-C₄-alkyl, C₁-C₄-alkenyl, OH, SH, CN, CF₃, O—CF₃, COOH,O—CH₂—COOH, C₁-C₆-alkoxy, C₁-C₆-alkylthio, C₃-C₇-cycloalkyl,COO—C₁-C₆-alkyl, CONH₂, CONH—C₁-C₆-alkyl, SO₂NH—C₁-C₆-alkyl,CON—(C₁-C₆-alkyl)₂, SO₂N—(C₁-C₆-alkyl)₂, NH₂, NH—C₁-C₆-alkyl,N—(C₁-C₆-alkyl)₂, NH—(C₁-C₄-alkyl-C₆-C₁₂-aryl), NH—CO—C₁-C₆-alkyl,NH—SO₂—C₁-C₆-alkyl, SO₂—C₁-C₆-alkyl, C₆-C₁₂-aryl, O—C₆-C₁₂-aryl,O—CH₂—C₆-C₁₂-aryl, CONH—C₆-C₁₂-aryl, SO₂NH—C₆-C₁₂-aryl,CONH—C₃-C₁₂-heterocyclyl, SO₂NH—C₃-C₁₂-heterocyclyl, SO₂—C₆-C₁₂-aryl,NH—SO₂—C₆-C₁₂-aryl, NH—CO—C₆-C₁₂-aryl, NH—SO₂—C₃-C₁₂-heterocyclyl,NH—CO—C₃-C₁₂-heterocyclyl and C₃-C₁₂-heterocyclyl, oxo (═O) being afurther substituent, wherein aryl and heterocyclyl in turn may beunsubstituted or substituted with 1, 2 or 3 substituents selected fromthe group consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl,C₁-C₄-alkoxy and C₁-C₄-haloalkoxy.

The term halogen denotes in each case fluorine, bromine, chlorine oriodine, in particular fluorine or chlorine.

C₁-C₄-Alkyl is a straight-chain or branched alkyl group having from 1 to4 carbon atoms. Examples of an alkyl group are methyl, C₂-C₄-alkyl suchas ethyl, n-propyl, iso-propyl, n-butyl, 2-butyl, iso-butyl ortert-butyl. C₁-C₂-Alkyl is methyl or ethyl, C₁-C₃-alkyl is additionallyn-propyl or isopropyl.

C₁-C₆-Alkyl is a straight-chain or branched alkyl group having from 1 to6 carbon atoms. Examples include methyl, C₂-C₄-alkyl as mentioned hereinand also pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl,2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl,1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl,4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl,2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl,1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl.

Halogenated C₁-C₄-alkyl is a straight-chain or branched alkyl grouphaving 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, morepreferably 1 or 2 carbon atoms, wherein at least one, e.g. 1, 2, 3, 4 orall of the hydrogen atoms are replaced by 1, 2, 3, 4 or a correspondingnumber of identical or different halogen atoms, such as inhalogenomethyl, dihalogenomethyl, trihalogenomethyl,(R)-1-halogenoethyl, (S)-1-halogenoethyl, 2-halogenoethyl,1,1-dihalogenoethyl, 2,2-dihalogenoethyl, 2,2,2-trihalogenoethyl,(R)-1-halogenopropyl, (S)-1-halogenopropyl, 2-halogenopropyl,3-halogenopropyl, 1,1-dihalogenopropyl, 2,2-dihalogenopropyl,3,3-dihalogenopropyl, 3,3,3-trihalogenopropyl,(R)-2-halogeno-1-methylethyl, (S)-2-halogeno-1-methylethyl,(R)-2,2-dihalogeno-1-methylethyl, (S)-2,2-dihalogeno-1-methylethyl,(R)-1,2-dihalogeno-1-methylethyl, (S)-1,2-dihalogeno-1-methylethyl,(R)-2,2,2-trihalogeno-1-methylethyl,(S)-2,2,2-trihalogeno-1-methylethyl, 2-halogeno-1-(halogenomethyl)ethyl,1-(dihalogenomethyl)-2,2-dihalogenoethyl, (R)-1-halogenobutyl,(S)-1-halogenobutyl, 2-halogenobutyl, 3-halogenobutyl, 4-halogenobutyl,1,1-dihalogenobutyl, 2,2-dihalogenobutyl, 3,3-dihalogenobutyl,4,4-dihalogenobutyl, 4,4,4-trihalogenobutyl, etc. Particular examplesinclude the fluorinated C₁-C₄ alkyl groups as defined, such astrifluoromethyl.

C₆-C₁₂-Aryl-C₁-C₄-alkyl is a straight-chain or branched alkyl grouphaving 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, morepreferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms,wherein one hydrogen atom is replaced by C₆-C₁₂-aryl, such as in benzyl.

Hydroxy-C₁-C₄-alkyl is a straight-chain or branched alkyl group having 1to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or2 carbon atoms, wherein one or two hydrogen atoms are replaced by one ortwo hydroxyl groups, such as in hydroxymethyl, (R)-1-hydroxyethyl,(S)-1-hydroxyethyl, 2-hydroxyethyl, (R)-1-hydroxypropyl,(S)-1-hydroxypropyl, 2-hydroxypropyl, 3-hydroxypropyl,(R)-2-hydroxy-1-methylethyl, (S)-2-hydroxy-1-methylethyl,2-hydroxy-1-(hydroxymethyl)ethyl, (R)-1-hydroxybutyl,(S)-1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl.

C₁-C₆-Alkoxy-C₁-C₄-alkyl is a straight-chain or branched alkyl grouphaving 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, morepreferably 1 or 2 carbon atoms, wherein one or two hydrogen atoms arereplaced by one or two alkoxy groups having 1 to 6, preferably 1 to 4,in particular 1 or 2 carbon atoms, such as in methoxymethyl,(R)-1-methoxyethyl, (S)-1-methoxyethyl, 2-methoxyethyl,(R)-1-methoxypropyl, (S)-1-methoxypropyl, 2-methoxypropyl,3-methoxypropyl, (R)-2-methoxy-1-methylethyl,(S)-2-methoxy-1-methylethyl, 2-methoxy-1-(methoxymethyl)ethyl,(R)-1-methoxybutyl, (S)-1-methoxybutyl, 2-methoxybutyl, 3-methoxybutyl,4-methoxybutyl, ethoxymethyl, (R)-1-ethoxyethyl, (S)-1-ethoxyethyl,2-ethoxyethyl, (R)-1-ethoxypropyl, (S)-1-ethoxypropyl, 2-ethoxypropyl,3-ethoxypropyl, (R)-2-ethoxy-1-methylethyl, (S)-2-ethoxy-1-methylethyl,2-ethoxy-1-(ethoxymethyl)ethyl, (R)-1-ethoxybutyl, (S)-1-ethoxybutyl,2-ethoxybutyl, 3-ethoxybutyl, 4-ethoxybutyl.

Amino-C₁-C₄-alkyl is a straight-chain or branched alkyl group having 1to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or2 carbon atoms, in particular 1 or two carbon atoms, wherein onehydrogen atom is replaced by an amino group, such as in aminomethyl,2-aminoethyl.

C₁-C₆-Alkylamino-C₁-C₄-alkyl is a straight-chain or branched alkyl grouphaving 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, morepreferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms,wherein one hydrogen atom is replaced by a C₁-C₆-alkylamino group, inparticular by a C₁-C₄-alkylamino group, such as in methylaminomethyl,ethylaminomethyl, n-propylaminomethyl, iso-propylaminomethyl,n-butylaminomethyl, 2-butylaminomethyl, iso-butylaminomethyl ortert-butylaminomethyl.

Di-C₁-C₆-Alkylamino-C₁-C₄-alkyl is a straight-chain or branched alkylgroup having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, morepreferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms,wherein one hydrogen atom is replaced by a di-C₁-C₆-Alkylamino group, inparticular by a di-C₁-C₄-alkylamino group, such as indimethylaminomethyl.

C₁-C₆-Alkylcarbonylamino-C₁-C₄-alkyl is a straight-chain or branchedalkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms,more preferably 1 or 2 carbon atoms, in particular 1 or two carbonatoms, wherein one hydrogen atom is replaced by aC₁-C₆-alkylcarbonylamino group, in particular by aC₁-C₄-alkylcarbonylamino group, such as in methylcarbonylaminomethyl,ethylcarbonylaminomethyl, n-propylcarbonylaminomethyl,iso-propylcarbonylaminomethyl, n-butylcarbonylaminomethyl,2-butylcarbonylaminomethyl, iso-butylcarbonylaminomethyl ortertbutylcarbonylaminomethyl.

C₁-C₆-Alkylaminocarbonylamino-C₁-C₄-alkyl is a straight-chain orbranched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 ortwo carbon atoms, wherein one hydrogen atom is replaced by aC₁-C₆-alkylaminocarbonylamino group, in particular by aC₁-C₄-alkylaminocarbonylamino group, such as inmethylaminocarbonylaminomethyl, ethylaminocarbonylaminomethyl,n-propylaminocarbonylaminomethyl, iso-propylaminocarbonylaminomethyl,n-butylaminocarbonylaminomethyl, 2-butylaminocarbonylaminomethyl,isobutylaminocarbonylaminomethyl or tert-butylaminocarbonylaminomethyl.

Di-C₁-C₆-alkylaminocarbonylamino-C₁-C₄-alkyl is a straight-chain orbranched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 ortwo carbon atoms, wherein one hydrogen atom is replaced by adi-C₁-C₆-alkylaminocarbonylamino group, in particular by adi-C₁-C₄-alkylaminocarbonylamino group, such as indimethylaminocarbonylaminomethyl, dimethylaminocarbonyl-aminoethyl,dimethylaminocarbonylaminon-propyl.

C₁-C₆-Alkylsulfonylamino-C₁-C₄-alkyl is a straight-chain or branchedalkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms,more preferably 1 or 2 carbon atoms, in particular 1 or two carbonatoms, wherein one hydrogen atom is replaced by aC₁-C₆-alkylsulfonylamino group, in particular by aC₁-C₄-alkylsulfonylamino group, such as in methylsulfonylaminomethyl,ethylsulfonylaminomethyl, n-propylsulfonylaminomethyl,isopropylsulfonylaminomethyl, n-butylsulfonylaminomethyl,2-butylsulfonylaminomethyl, isobutylsulfonylaminomethyl ortert-butylsulfonylaminomethyl.

(C₆-C₁₂-Aryl-C₁-C₆-alkyl)amino-C₁-C₄ alkyl is a straight-chain orbranched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 ortwo carbon atoms, wherein one hydrogen atom is replaced by a(C₆-C₁₂-aryl-C₁-C₆-alkyl)amino group, in particular a(C₆-C₁₂-aryl-C₁-C₂-alkyl)amino group, such as in benzylaminomethyl.

C₃-C₁₂-Heterocyclyl-C₁-C₄-alkyl is a straight-chain or branched alkylgroup having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, morepreferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms,wherein one hydrogen atom is replaced by C₃-C₁₂-heterocyclyl, such as inN-pyrrolidinylmethyl, N-piperidinylmethyl, N-morpholinylmethyl.

C₃-C₁₂-Cycloalkyl is a cycloaliphatic radical having from 3 to 12 carbonatoms. In particular, 3 to 6 carbon atoms form the cyclic structure,such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The cyclicstructure may be unsubstituted or may carry 1, 2, 3 or 4 C₁-C₄ alkylradicals, preferably one or more methyl radicals.

Carbonyl is >C═O.

C₁-C₆-Alkylcarbonyl is a radical of the formula R—C(O)—, wherein R is analkyl radical having from 1 to 6, preferably from 1 to 4, in particular1 or 2 carbon atoms as defined herein. Examples include acetyl,propionyl, n-butyryl, 2-methylpropionyl, pivaloyl.

Halogenated C₁-C₆-alkylcarbonyl is C₁-C₆-alkylcarbonyl as definedherein, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogenatoms are replaced by 1, 2, 3, 4 or a corresponding number of identicalor different halogen atoms. Examples include fluoromethylcarbonyl,difluoromethylcarbonyl, trifluoromethylcarbonyl. Further examples are1,1,1-trifluoroeth-2-ylcarbonyl, 1,1,1-trifluoroprop-3-ylcarbonyl.

C₆-C₁₂-Arylcarbonyl is a radical of the formula R—C(O)—, wherein R is anaryl radical having from 6 to 12 carbon atoms as defined herein.Examples include benzoyl.

C₁-C₆-Alkoxycarbonyl is a radical of the formula R—O—C(O)—, wherein R isan alkyl radical having from 1 to 6, preferably from 1 to 4, inparticular 1 or 2 carbon atoms as defined herein. Examples includemethoxycarbonyl and tert-butyloxycarbonyl.

Halogenated C₁-C₆-alkoxycarbonyl is a C₁-C₆-alkoxycarbonyl as definedherein, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogenatoms are replaced by 1, 2, 3, 4 or a corresponding number of identicalor different halogen atoms.

C₆-C₁₂-Aryloxycarbonyl is a radical of the formula R—O—C(O)—, wherein Ris an aryl radical having from 6 to 12 carbon atoms as defined herein.Examples include phenoxycarbonyl.

Cyano is —C≡N.

Aminocarbonyl is NH₂C(O)—.

C₁-C₆-Alkylaminocarbonyl is a radical of the formula R—NH—C(O)—, whereinR is an alkyl radical having from 1 to 6, preferably from 1 to 4, inparticular 1 or 2 carbon atoms as defined herein. Examples includemethylaminocarbonyl.

(Halogenated C₁-C₄-alkyl)aminocarbonyl is a C₁-C₄-alkylaminocarbonyl asdefined herein, wherein at least one, e.g. 1, 2, 3, 4 or all of thehydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number ofidentical or different hydrogen atoms.

C₆-C₁₂-Arylaminocarbonyl is a radical of the formula R—NH—C(O)—, whereinR is an aryl radical having from 6 to 12 carbon atoms as defined herein.Examples include phenylaminocarbonyl.

C₂-C₆-Alkenyl is a singly unsaturated hydrocarbon radical having 2, 3,4, 5 or 6 carbon atoms, e.g. vinyl, allyl (2-propen-1-yl),1-propen-1-yl, 2-propen-2-yl, methallyl(2-methylprop-2-en-1-yl) and thelike. C₃-C₅-Alkenyl is, in particular, allyl, 1-methylprop-2-en-1-yl,2-buten-1-yl, 3-buten-1-yl, methallyl, 2-penten-1-yl, 3-penten-1-yl,4-penten-1-yl, 1-methylbut-2-en-1-yl or 2-ethylprop-2-en-1-yl.

C₂-C₆-Alkynyl is a singly unsaturated hydrocarbon radical having 2, 3,4, 5 or 6 carbon atoms, e.g. ethynyl, 2-propyn-1-yl, 1-propyn-1-yl,2-propyn-2-yl and the like. C₃-C₅-Alkynyl is, in particular,2-propyn-1-yl, 2-butyn-1-yl, 3-butyn-1-yl, 2-pentyn-1-yl, 3-pentyn-1-yl,4-pentyn-1-yl.

C₁-C₄-Alkylene is straight-chain or branched alkylene group having from1 to 4 carbon atoms. Examples include methylene and ethylene. A furtherexample is propylene.

C₂-C₄-Alkenylene is straight-chain or branched alkenylene group havingfrom 2 to 4 carbon atoms.

C₂-C₄-Alkynylene is straight-chain or branched alkynylene group havingfrom 2 to 4 carbon atoms. Examples include propynylene.

C₆-C₁₂-Aryl is a 6- to 12-membered, in particular 6- to 10-membered,aromatic cyclic radical. Examples include phenyl and naphthyl.

C₃-C₁₂-Arylene is an aryl diradical. Examples include phen-1,4-ylene andphen-1,3-ylene.

Hydroxy is —OH.

C₁-C₆-Alkoxy is a radical of the formula R—O—, wherein R is astraight-chain or branched alkyl group having from 1 to 6, in particular1 to 4 carbon atoms. Examples include methoxy, ethoxy, n-propoxy,isopropoxy, n-butoxy, 2-butoxy, iso-butoxy (2-methylpropoxy),tert.-butoxy pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy,2,2-dimethylpropoxy, 1-ethylpropoxy, hexyloxy, 1,1-dimethylpropoxy,1,2-dimethylpropoxy, 1-methylpentyloxy, 2-methylpentyloxy,3-methylpentyloxy, 4-methylpentyloxy, 1,1-dimethylbutyloxy,1,2-dimethylbutyloxy, 1,3-dimethylbutyloxy, 2,2-dimethylbutyloxy,2,3-dimethylbutyloxy, 3,3-dimethylbutyloxy, 1-ethylbutyloxy,2-ethylbutyloxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy,1-ethyl-1-methylpropoxy and 1-ethyl-2-methylpropoxy.

Halogenated C₁-C₆-alkoxy is a straight-chain or branched alkoxy grouphaving from 1 to 6, preferably from 1 to 4, in particular 1 or 2 carbonatoms, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogenatoms are replaced by 1, 2, 3, 4 or a corresponding number of identicalor different halogen atoms, such as in halogenomethoxy,dihalogenomethoxy, trihalogenomethoxy, (R)-1-halogenoethoxy,(S)-1-halogenoethoxy, 2-halogenoethoxy, 1,1-dihalogenoethoxy,2,2-dihalogenoethoxy, 2,2,2-trihalogenoethoxy, (R)-1-halogenopropoxy,(S)-1-halogenopropoxy, 2-halogenopropoxy, 3-halogenopropoxy,1,1-dihalogenopropoxy, 2,2-dihalogenopropoxy, 3,3-dihalogenopropoxy,3,3,3-trihalogenopropoxy, (R)-2-halogeno-1-methylethoxy,(S)-2-halogeno-1-methylethoxy, (R)-2,2-dihalogeno-1-methylethoxy,(S)-2,2-dihalogeno-1-methylethoxy, (R)-1,2-dihalogeno-1-methylethoxy,(S)-1,2-dihalogeno-1-methylethoxy, (R)-2,2,2-trihalogeno-1-methylethoxy,(S)-2,2,2-trihalogeno-1-methylethoxy,2-halogeno-1-(halogenomethyl)ethoxy,1-(dihalogenomethyl)-2,2-dihalogenoethoxy, (R)-1-halogenobutoxy,(S)-1-halogenobutoxy, 2-halogenobutoxy, 3-halogenobutoxy,4-halogenobutoxy, 1,1-dihalogenobutoxy, 2,2-dihalogenobutoxy,3,3-dihalogenobutoxy, 4,4-dihalogenobutoxy, 4,4,4-trihalogenobutoxy,etc. Particular examples include the fluorinated C₁-C₄ alkoxy groups asdefined, such as trifluoromethoxy.

C₁-C₆-Hydroxyalkoxy is an alkoxy radical having from 1 to 6, preferablyfrom 1 to 4 carbon atoms as defined herein, wherein one or two hydrogenatoms are replaced by hydroxy. Examples include 2-hydroxyethoxy,3-hydroxypropoxy, 2-hydroxypropoxy, 1-methyl-2-hydroxyethoxy and thelike.

C₁-C₆-Alkoxy-C₁-C₄-alkoxy is an alkoxy radical having from 1 to 4 carbonatoms, preferably 1 or 2 carbon atoms as defined herein, wherein one ortwo hydrogen atoms are replaced by one or two alkoxy radicals havingfrom 1 to 6, preferably from 1 to 4 carbon atoms as defined herein.Examples include methoxymethoxy, 2-methoxyethoxy, 1-methoxyethoxy,3-methoxypropoxy, 2-methoxypropoxy, 1-methyl-1-methoxyethoxy,ethoxymethoxy, 2-ethoxyethoxy, 1-ethoxyethoxy, 3-ethoxypropoxy,2-ethoxypropoxy, 1-methyl-1-ethoxyethoxy and the like.

Amino-C₁-C₄-alkoxy is an alkoxy radical having from 1 to 4, preferably 1or 2 carbon atoms as defined herein, wherein one hydrogen atom isreplaced by an amino group. Examples include 2-aminoethoxy.

C₁-C₆-Alkylamino-C₁-C₄-alkoxy is an alkoxy radical having from 1 to 4,preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogenatom is replaced by an alkylamino group having from 1 to 6, preferablyfrom 1 to 4 carbon atoms as defined herein. Examples includemethylaminomethoxy, ethylaminomethoxy, n-propylaminomethoxy,isopropylaminomethoxy, n-butylaminomethoxy, 2-butylaminomethoxy,isobutylaminomethoxy, tert-butylaminomethoxy, 2-(methylamino)ethoxy,2-(ethylamino)ethoxy, 2-(n-propylamino)ethoxy,2-(iso-propylamino)ethoxy, 2-(n-butylamino)ethoxy,2-(2-butylamino)ethoxy, 2-(iso-butylamino)ethoxy,2-(tert-butylamino)ethoxy.

Di-C₁-C₆-alkylamino-C₁-C₄-alkoxy is an alkoxy radical having from 1 to4, preferably 1 or 2 carbon atoms as defined herein, wherein onehydrogen atom is replaced by a dialkylamino group having from 1 to 6,preferably from 1 to 4 carbon atoms as defined herein. Examples includedimethylaminomethoxy, diethylaminomethoxy, N-methyl-N-ethylamino)ethoxy,2-(dimethylamino)ethoxy, 2-(diethylamino)ethoxy,2-(N-methyl-N-ethylamino)ethoxy.

C₁-C₆-Alkylcarbonylamino-C₁-C₄-alkoxy is an alkoxy radical having from 1to 4, preferably 1 or 2 carbon atoms as defined herein, wherein onehydrogen atom is replaced by an alkylcarbonylamino group wherein thealkyl group has from 1 to 6, preferably from 1 to 4 carbon atoms asdefined herein. Examples include methylcarbonylaminomethoxy,ethylcarbonylaminomethoxy, n-propylcarbonylaminomethoxy,isopropylcarbonylaminomethoxy, n-butylcarbonylaminomethoxy,2-butylcarbonylaminomethoxy, iso-butylcarbonylaminomethoxy,tert-butylcarbonylaminomethoxy, 2-(methylcarbonylamino)ethoxy,2-(ethylcarbonylamino)ethoxy, 2-(n-propylcarbonylamino)ethoxy,2-(iso-propylcarbohylamino)ethoxy, 2-(n-butylcarbonylamino)ethoxy,2-(2-butylcarbonylamino)ethoxy, 2-(iso-butylcarbonylamino)ethoxy,2-(tert-butylcarbonylamino)ethoxy.

C₆-C₁₂-Arylcarbonylamino-C₁-C₄-alkoxy is an alkoxy radical having from 1to 4, preferably 1 or 2 carbon atoms as defined herein, wherein onehydrogen atom is replaced by a C₆-C₁₂-arylcarbonylamino group as definedherein. Examples include 2-(benzoylamino)ethoxy.

C₁-C₆-Alkoxycarbonylamino-C₁-C₄-alkoxy is an alkoxy radical having from1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein onehydrogen atom is replaced by an alkoxycarbonylamino group wherein thealkoxy group has from 1 to 6, preferably from 1 to 4 carbon atoms asdefined herein. Examples include methoxycarbonylaminomethoxy,ethoxycarbonylaminomethoxy, n-propoxycarbonylaminomethoxy,isopropoxycarbonylaminomethoxy, n-butoxycarbonylaminomethoxy,2-butoxycarbonylaminomethoxy, iso-butoxycarbonylaminomethoxy,tert-butoxycarbonylaminomethoxy, 2-(methoxycarbonylamino)ethoxy,2-(ethoxycarbonylamino)ethoxy, 2-(n-propoxycarbonylamino)ethoxy,2-(iso-propoxycarbonylamino)ethoxy, 2-(n-butoxycarbonylamino)ethoxy,2-(2-butoxycarbonylamino)ethoxy, 2-(isobutoxycarbonylamino)ethoxy,2-(tert-butoxycarbonylamino)ethoxy.

C₂-C₆-Alkenyloxy is a radical of the formula R—O—, wherein R is astraight-chain or branched alkenyl group having from 2 to 6, inparticular 2 to 4 carbon atoms. Examples include vinyloxy, allyloxy(2-propen-1-yloxy), 1-propen-1-yloxy, 2-propen-2-yloxy, methallyloxy(2-methylprop-2-en-1-yloxy) and the like. C₃-C₅-Alkenyloxy is, inparticular, allyloxy, 1-methylprop-2-en-1-yloxy, 2-buten-1-yloxy,3-buten-1-yloxy, methallyloxy, 2-penten-1-yloxy, 3-penten-1-yloxy,4-penten-1-yloxy, 1-methylbut-2-en-1-yloxy or 2-ethylprop-2-en-1-yloxy.

C₆-C₁₂-Aryl-C₁-C₄-alkoxy is an alkoxy radical having from 1 to 4,preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogenatom is replaced by a C₆-C₁₂-aryl group as defined herein. Examplesinclude benzyloxy.

C₁-C₆-Alkylsulfonylamino-C₁-C₄-alkoxy is an alkoxy radical having from 1to 4, preferably 1 or 2 carbon atoms as defined herein, wherein onehydrogen atom is replaced by an alkylsulfonylamino group having from 1to 6, preferably from 1 to 4 carbon atoms as defined herein. Examplesinclude 2-(methylsulfonylamino)ethoxy, 2-(ethylsulfonylamino)ethoxy,2-[(2-methylpropyl)sulfonylamino]ethoxy.

(Halogenated C₁-C₆-alkyl)sulfonylamino-C₁-C₄-alkoxy is an alkoxy radicalhaving from 1 to 4, preferably 1 or 2 carbon atoms as defined herein,wherein one hydrogen atom is replaced by an alkylsulfonylamino grouphaving from 1 to 6, preferably from 1 to 4 carbon atoms as definedherein, wherein the alkyl group is halogenated. Examples include2-(trifluoromethylsulfonylamino)ethoxy.

C₆-C₁₂-Arylsulfonylamino-C₁-C₄-alkoxy is an alkoxy radical having from 1to 4, preferably 1 or 2 carbon atoms as defined herein, wherein onehydrogen atom is replaced by a C₆-C₁₂-arylsulfonylamino group as definedherein. Examples include 2-(phenylsulfonylamino)ethoxy,2-(naphthylsulfonylamino)ethoxy.

(C₆-C₁₂-Aryl-C₁-C₆-alkyl)sulfonylamino-C₁-C₄-alkoxy is an alkoxy radicalhaving from 1 to 4, preferably 1 or 2 carbon atoms as defined herein,wherein one hydrogen atom is replaced by a(C₆-C₁₂-aryl-C₁-C₆-alkyl)sulfonylamino group, preferably by a(C₆-C₁₂-aryl-C₁-C₂-alkyl)sulfonylamino group. Examples include2-(benzylsulfonylamino)ethoxy.

C₃-C₁₂-Heterocyclylsulfonylamino-C₁-C₄-alkoxy is an alkoxy radicalhaving from 1 to 4, preferably 1 or 2 carbon atoms as defined herein,wherein one hydrogen atom is replaced by aC₃-C₁₂-heterocyclylsulfonylamino group as defined herein. Examplesinclude 2-(pyridin-3-yl-sulfonylamino)ethoxy.

C₃-C₁₂-Heterocyclyl-C₁-C₄-alkoxy is an alkoxy radical having from 1 to4, preferably 1 or 2 carbon atoms as defined herein, wherein onehydrogen atom is replaced by a C₃-C₁₂-heterocyclyl group as definedherein. Examples include 2-(N-pyrrolidinyl)ethoxy,2-(N-morpholinyl)ethoxy and 2-(N-imidazolyl)ethoxy.

C₁-C₂-Alkylenedioxo is a radical of the formula —O—R—O—, wherein R is astraight-chain or branched alkylene group having from 1 or 2 carbonatoms as defined herein. Examples include methylenedioxo.

C₆-C₁₂-Aryloxy is a radical of the formula R—O—, wherein R is an arylgroup having from 6 to 12, in particular 6 carbon atoms as definedherein. Examples include phenoxy.

C₃-C₁₂-Heterocyclyloxy is a radical of the formula R—O—, wherein R is aC₃-C₁₂-heterocyclyl group having from 3 to 12, in particular from 3 to 7carbon atoms as defined herein. Examples include pyridin-2-yloxy.

C₁-C₆-Alkylthio is a radical of the formula R—S—, wherein R is an alkylradical having from 1 to 6, preferably from 1 to 4 carbon atoms asdefined herein. Examples include methylthio, ethylthio, propylthio,butylthio, pentylthio, 1-methylbutylthio, 2-methylbutylthio,3-methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexylthio,1,1-dimethylpropylthio, 1,2-dimethylpropylthio, 1-methylpentylthio,2-methylpentylthio, 3-methylpentylthio, 4-methylpentylthio,1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3-dimethylbutylthio,2,2-dimethylbutylthio, 2,3-dimethylbutylthio, 3,3-dimethylbutylthio,1-ethylbutylthio, 2-ethylbutylthio, 1,1,2-trimethylpropylthio,1,2,2-trimethylpropylthio, 1-ethyl-1-methylpropyl and1-ethyl-2-methylpropyl.

Halogenated C₁-C₅-alkylthio is a radical of the formula R—S—, wherein Ris a halogenated alkyl radical having from 1 to 6, preferably from 1 to4 carbon atoms as defined herein. Examples include halogenomethylthio,dihalogenomethylthio, trihalogenomethylthio, (R)-1-halogenoethylthio,(S)-1-halogenoethylthio, 2-halogenoethylthio, 1,1-dihalogenoethylthio,2,2-dihalogenoethylthio, 2,2,2-trihalogenoethylthio,(R)-1-halogenopropylthio, (S)-1-halogenopropylthio,2-halogenopropylthio, 3-halogenopropylthio, 1,1-dihalogenopropylthio,2,2-dihalogenopropylthio, 3,3-dihalogenopropylthio,3,3,3-trihalogenopropylthio, (R)-2-halogeno-1-methylethylthio,(S)-2-halogeno-1-methylethylthio, (R)-2,2-dihalogeno-1-methylethylthio,(S)-2,2-dihalogeno-1-methylethylthio,(R)-1,2-dihalogeno-1-methylethylthio,(S)-1,2-dihalogeno-1-methylethylthio,(R)-2,2,2-trihalogeno-1-methylethylthio,(S)-2,2,2-trihalogeno-1-methylethylthio,2-halogeno-1-(halogenomethyl)ethylthio,1-(dihalogenomethyl)-2,2-dihalogenoethylthio, (R)-1-halogenobutylthio,(S)-1-halogenobutylthio, 2-halogenobutylthio, 3-halogenobutylthio,4-halogenobutylthio, 1,1-dihalogenobutylthio, 2,2-dihalogenobutylthio,3,3-dihalogenobutylthio, 4,4-dihalogenobutylthio,4,4,4-trihalogeriobutylthio, etc. Particular examples include thefluorinated C₁-C₄ alkylthio groups as defined, such astrifluoromethylthio.

C₁-C₆-Alkylsulfinyl is a radical of the formula R—S(O)—, wherein R is analkyl radical having from 1 to 6, preferably from 1 to 4 carbon atoms asdefined herein. Examples include methylsulfinyl, ethylsulfinyl,propylsulfinyl, butylsulfinyl, pentylsulfinyl, 1-methylbutylsulfinyl,2-methylbutylsulfinyl, 3-methylbutylsulfinyl,2,2-dimethylpropylsulfinyl, 1-ethylpropylsulfinyl, hexylsulfinyl,1,1-dimethylpropylsulfinyl, 1,2-dimethylpropylsulfinyl,1-methylpentylsulfinyl, 2-methylpentylsulfinyl, 3-methylpentylsulfinyl,4-methylpentylsulfinyl, 1,1-dimethylbutylsulfinyl,1,2-dimethylbutylsulfinyl, 1,3-dimethylbutylsulfinyl,2,2-dimethylbutylsulfinyl, 2,3-dimethylbutylsulfinyl,3,3-dimethylbutylsulfinyl, 1-ethylbutylsulfinyl, 2-ethylbutylsulfinyl,1,1,2-trimethylpropylsulfinyl, 1,2,2-trimethylpropylsulfinyl,1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl.

C₁-C₆-Alkylsulfonyl is a radical of the formula R—S(O)₂—, wherein R isan alkyl radical having from 1 to 6, preferably from 1 to 4 carbon atomsas defined herein. Examples include methylsulfonyl, ethylsulfonyl,propylsulfonyl, butylsulfonyl, pentylsulfonyl, 1-methylbutylsulfonyl,2-methylbutylsulfonyl, 3-methylbutylsulfonyl,2,2-dimethylpropylsulfonyl, 1-ethylpropylsulfonyl, hexylsulfonyl,1,1-dimethylpropylsulfonyl, 1,2-dimethylpropylsulfonyl,1-methylpentylsulfonyl, 2-methylpentylsulfonyl, 3-methylpentylsulfonyl,4-methylpentylsulfonyl, 1,1-dimethylbutylsulfonyl,1,2-dimethylbutylsulfonyl, 1,3-dimethylbutylsulfonyl,2,2-dimethylbutylsulfonyl, 2,3-dimethylbutylsulfonyl,3,3-dimethylbutylsulfonyl, 1-ethylbutylsulfonyl, 2-ethylbutylsulfonyl,1,1,2-trimethylpropylsulfonyl, 1,2,2-trimethylpropylsulfonyl,1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl.

(Halogenated C₁-C₆-alkyl)sulfonyl is a C₁-C₆-alkylsulfonyl as definedherein, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogenatoms are replaced by 1, 2, 3, 4 or a corresponding number of identicalor different halogen atoms.

C₆-C₁₂-Arylsulfonyl is a radical of the formula R—S(O)₂—, wherein R isan aryl radical having from 6 to 12 carbon atoms as defined herein.Examples include phenylsulfonyl.

(C₆-C₁₂-Aryl-C₁-C₄-alkyl)sulfonyl is a radical of the formula R—S(O)₂—,wherein R is a C₆-C₁₂-aryl-C₁-C₄-alkyl radical, in particular aC₆-C₁₂-aryl-C₁-C₂-alkyl radical as defined herein. Examples includebenzylsulfonyl.

C₃-C₁₂-Heterocyclylsulfonyl is a radical of the formula R—S(O)₂—,wherein R is C₃-C₁₂-heterocyclyl as defined herein.

Aminosulfonyl is NH₂—S(O)₂—.

C₁-C₆-Alkylaminosulfonyl is a radical of the formula R—NH—S(O)₂— whereinR is an alkyl radical having from 1 to 6, preferably from 1 to 4 carbonatoms as defined herein. Examples include methylaminosulfonyl,ethylaminosulfonyl, n-propylaminosulfonyl, isopropylaminosulfonyl,n-butylaminosulfonyl, 2-butylaminosulfonyl, iso-butylaminosulfonyl,tert-butylaminosulfonyl.

Di-C₁-C₆-alkylaminosulfonyl is a radical of the formula RR′N—S(O)₂—wherein R and R′ are independently of each other an alkyl radical havingfrom 1 to 6, preferably from 1 to 4 carbon atoms as defined herein.Examples include dimethylaminosulfonyl, diethylaminosulfonyl,N-methyl-N-ethylaminosulfonyl.

C₆-C₁₂-Arylaminosulfonyl is a radical of the formula R—NH—S(O)₂— whereinR is an aryl radical having from 6 to 12, preferably 6 carbon atoms asdefined herein.

Amino is NH₂.

C₁-C₆-Alkylamino is a radical of the formula R—NH— wherein R is an alkylradical having from 1 to 6, in particular from 1 to 4 carbon atoms asdefined herein. Examples include methylamino, ethylamino, n-propylamino,iso-propylamino, n-butylamino, 2-butylamino, iso-butylamino,tert-butylamino.

(Halogenated C₁-C₆-alkyl)amino is a C₁-C₆-alkylamino as defined herein,wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms arereplaced by 1, 2, 3, 4 or a corresponding number of identical ordifferent halogen atoms.

Di-C₁-C₆-alkylamino is a radical of the formula RR′N— wherein R and R′are independently of each other an alkyl radical having from 1 to 6, inparticular from 1 to 4 carbon atoms as defined herein. Examples includedimethylamino, diethylamino, N-methyl-N-ethylamino.

Di-(halogenated C₁-C₆-alkyl)amino is a di-C₁-C₆-alkylamino as definedherein, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogenatoms are replaced by 1, 2, 3, 4 or a corresponding number of identicalor different halogen atoms.

C₁-C₆-Alkylcarbonylamino is a radical of the formula R—C(O)—NH—, whereinR is an alkyl radical having from 1 to 6, in particular from 1 to 4carbon atoms as defined herein. Examples include acetamido(methylcarbonylamino), propionamido, n-butyramido, 2-methylpropionamido(isopropylcarbonylamino), 2,2-dimethylpropionamido and the like.

(Halogenated C₁-C₆-alkyl)carbonylamino is a C₁-C₆-alkylcarbonylamino asdefined herein, wherein at least one, e.g. 1, 2, 3, 4 or all of thehydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number ofidentical or different halogen atoms.

C₆-C₁₂-Arylcarbonylamino is a radical of the formula R—C(O)—NH—, whereinR is an aryl radical having from 6 to 12 carbon atoms as defined herein.Examples include phenylcarbonylamino.

C₂-C₆-Alkenylamino is a radical of the formula R—NH—, wherein R is astraight-chain or branched alkenyl group having from 2 to 6, inparticular 2 to 4 carbon atoms. Examples include vinylamino, allylamino(2-propen-1-ylamino), 1-propen-1-ylamino, 2-propen-2-ylamino,methallylamino (2-methylprop-2-en-1-ylamino) and the like.C₃-C₅-Alkenylamino is, in particular, allylamino,1-methylprop-2-en-1-ylamino, 2-buten-1-ylamino, 3-buten-1-ylamino,methallylamino, 2-penten-1-ylamino, 3-penten-1-ylamino,4-penten-1-ylamino, 1-methylbut-2-en-1-ylamino or2-ethylprop-2-en-1-ylamino.

C₁-C₆-Alkylsulfonylamino is a radical of the formula R—S(O)₂—NH—,wherein R is an alkyl radical having from 1 to 6, in particular from 1to 4 carbon atoms as defined herein. Examples includemethylsulfonylamino, ethylsulfonylamino, n-propylsulfonylamino,isopropylsulfonylamino, n-butylsulfonylamino, 2-butylsulfonylamino,iso-butylsulfonylamino, tert-butylsulfonylamino.

(Halogenated C₁-C₆ alkyl)sulfonylamino is a C₁-C₆-alkylsulfonylamino asdefined herein, wherein at least one, e.g. 1, 2, 3, 4 or all of thehydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number ofidentical or different halogen atoms.

C₆-C₁₂-Arylsulfonylamino is a radical of the formula R—S(O)₂—NH—,wherein R is an aryl radical having from 6 to 12 carbon atoms as definedherein. Examples include phenylsulfonylamino.

Nitro is —NO₂.

C₃-C₁₂-Heterocyclyl is a 3- to 12-membered heterocyclic radicalincluding a saturated heterocyclic radical, which generally has 3, 4, 5,6, or 7 ring forming atoms (ring members), an unsaturated non-aromaticheterocyclic radical, which generally has 5, 6 or 7 ring forming atoms,and a heteroaromatic radical (hetaryl), which generally has 5, 6 or 7ring forming atoms. The heterocyclic radicals may be bound via a carbonatom (C-bound) or a nitrogen atom (N-bound). Preferred heterocyclicradicals comprise 1 nitrogen atom as ring member atom and optionally 1,2 or 3 further heteroatoms as ring members, which are selected,independently of each other from O, S and N. Likewise preferredheterocyclic radicals comprise 1 heteroatom as ring member, which isselected from O, S and N, and optionally 1, 2 or 3 further nitrogenatoms as ring members.

Examples of C₃-C₁₂-heterocyclyl include:

C- or N-bound 3-4-membered, saturated rings, such as 2-oxiranyl,2-oxetanyl, 3-oxetanyl, 2-aziridinyl, 3-thiethanyl, 1-azetidinyl,2-azetidinyl, 3-azetidinyl;

C-bound, 5-membered, saturated rings, such as tetrahydrofuran-2-yl,tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl,tetrahydropyrrol-2-yl, tetrahydropyrrol-3-yl, tetrahydropyrazol-3-yl,tetrahydro-pyrazol-4-yl, tetrahydroisoxazol-3-yl,tetrahydroisoxazol-4-yl, tetrahydroisoxazol-5-yl, 1,2-oxathiolan-3-yl,1,2-oxathiolan-4-yl, 1,2-oxathiolan-5-yl, tetrahydroisothiazol-3-yl,tetrahydroisothiazol-4-yl, tetrahydroisothiazol-5-yl,1,2-dithiolan-3-yl, 1,2-dithiolan-4-yl, tetrahydroimidazol-2-yl,tetrahydroimidazol-4-yl, tetrahydrooxazol-2-yl, tetrahydrooxazol-4-yl,tetrahydrooxazol-5-yl, tetrahydrothiazol-2-yl, tetrahydrothiazol-4-yl,tetrahydrothiazol-5-yl, 1,3-dioxolan-2-yl, 1,3-dioxolan-4-yl,1,3-oxathiolan-2-yl, 1,3-oxathiolan-4-yl, 1,3-oxathiolan-5-yl,1,3-dithiolan-2-yl, 1,3-dithiolan-4-yl, 1,3,2-dioxathiolan-4-yl;

C-bound, 6-membered, saturated rings, such as tetrahydropyran-2-yl,tetrahydropyran-3-yl, tetrahydropyran-4-yl, piperidin-2-yl,piperidin-3-yl, piperidin-4-yl, tetrahydrothiopyran-2-yl,tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, 1,3-dioxan-2-yl,1,3-dioxan-4-yl, 1,3-dioxan-5-yl, 1,4-dioxan-2-yl, 1,3-dithian-2-yl,1,3-dithian-4-yl, 1,3-dithian-5-yl, 1,4-dithian-2-yl, 1,3-oxathian-2-yl,1,3-oxathian-4-yl, 1,3-oxathian-5-yl, 1,3-oxathian-6-yl,1,4-oxathian-2-yl, 1,4-oxathian-3-yl, 1,2-dithian-3-yl,1,2-dithian-4-yl, hexhydropyrimidin-2-yl, hexahydropyrimidin-4-yl,hexahydropyrimidin-5-yl, hexahydropyrazin-2-yl, hexahydropyridazin-3-yl,hexahydropyridazin-4-yl, tetrahydro-1,3-oxazin-2-yl,tetrahydro-1,3-oxazin-4-yl, tetrahydro-1,3-oxazin-5-yl,tetrahydro-1,3-oxazin-6-yl, tetrahydro-1,3-thiazin-2-yl,tetrahydro-1,3-thiazin-4-yl, tetrahydro-1,3-thiazin-5-yl,tetrahydro-1,3-thiazin-6-yl, tetrahydro-1,4-thiazin-2-yl,tetrahydro-1,4-thiazin-3-yl, tetrahydro-1,4-oxazin-2-yl,tetrahydro-1,4-oxazin-3-yl, tetrahydro-1,2-oxazin-3-yl,tetrahydro-1,2-oxazin-4-yl, tetrahydro-1,2-oxazin-5-yl,tetrahydro-1,2-oxazin-6-yl;

N-bound, 5-membered, saturated rings, such as tetrahydropyrrol-1-yl(pyrrolidin-1-yl), tetrahydropyrazol-1-yl, tetrahydroisoxazol-2-yl,tetrahydroisothiazol-2-yl, tetrahydroimidazol-1-yl,tetrahydrooxazol-3-yl, tetrahydrothiazol-3-yl;

N-bound, 6-membered, saturated rings, such as piperidin-1-yl,hexahydropyrimidin-1-yl, hexahydropyrazin-1-yl (piperazin-1-yl),hexahydropyridazin-1-yl, tetrahydro-1,3-oxazin-3-yl,tetrahydro-1,3-thiazin-3-yl, tetrahydro-1,4-thiazin-4-yl,tetrahydro-1,4-oxazin-4-yl (morpholin-1-yl), tetrahydro-1,2-oxazin-2-yl;

C-bound, 5-membered, partially unsaturated rings, such as2,3-dihydrofuran-2-yl, 2,3-dihydrofuran-3-yl, 2,5-dihydrofuran-2-yl,2,5-di-hydrofuran-3-yl, 4,5-dihydrofuran-2-yl, 4,5-dihydrofuran-3-yl,2,3-dihydro-thien-2-yl, 2,3-dihydrothien-3-yl, 2,5-dihydrothien-2-yl,2,5-dihydrothien-3-yl, 4,5-dihydrothien-2-yl, 4,5-dihydrothien-3-yl,2,3-dihydro-1H-pyrrol-2-yl, 2,3-dihydro-1H-pyrrol-3-yl,2,5-dihydro-1H-pyrrol-2-yl, 2,5-dihydro-1H-pyrrol-3-yl,4,5-dihydro-1H-pyrrol-2-yl, 4,5-dihydro-1H-pyrrol-3-yl,3,4-dihydro-2H-pyrrol-2-yl, 3,4-dihydro-2H-pyrrol-3-yl,3,4-dihydro-5H-pyrrol-2-yl, 3,4-dihydro-5H-pyrrol-3-yl,4,5-dihydro-1H-pyrazol-3-yl, 4,5-dihydro-1H-pyrazol-4-yl,4,5-dihydro-1H-pyrazol-5-yl, 2,5-dihydro-1H-pyrazol-3-yl,2,5-dihydro-1H-pyrazol-4-yl, 2,5-dihydro-1H-pyrazol-5-yl,4,5-dihydroisoxazol-3-yl, 4,5-dihydroisoxazol-4-yl,4,5-dihydroisoxazol-5-yl, 2,5-dihydroisoxazol-3-yl,2,5-dihydroisoxazol-4-yl, 2,5-dihydroisoxazol-5-yl,2,3-dihydroisoxazol-3-yl, 2,3-dihydroisoxazol-4-yl,2,3-dihydroisoxazol-5-yl, 4,5-dihydroisothiazol-3-yl,4,5-dihydroisothiazol-4-yl, 4,5-dihydroisothiazol-5-yl,2,5-dihydroisothiazol-3-yl, 2,5-dihydroisothiazol-4-yl,2,5-dihydroisothiazol-5-yl, 2,3-dihydroisothiazol-3-yl,2,3-dihydroisothiazol-4-yl, 2,3-dihydroisothiazol-5-yl,4,5-dihydro-1H-imidazol-2-yl, 4,5-dihydro-1H-imidazol-4-yl,4,5-dihydro-1H-imidazol-5-yl, 2,5-dihydro-1H-imidazol-2-yl,2,5-dihydro-1H-imidazol-4-yl, 2,5-dihydro-1H-imidazol-5-yl,2,3-dihydro-1H-imidazol-2-yl, 2,3-dihydro-1H-imidazol-4-yl,4,5-dihydro-oxazol-2-yl, 4,5-dihydrooxazol-4-yl, 4,5-dihydrooxazol-5-yl,2,5-dihydrooxazol-2-yl, 2,5-dihydrooxazol-4-yl, 2,5-dihydrooxazol-5-yl,2,3-dihydrooxazol-2-yl, 2,3-dihydrooxazol-4-yl, 2,3-dihydrooxazol-5-yl,4,5-dihydrothiazol-2-yl, 4,5-dihydrothiazol-4-yl,4,5-dihydrothiazol-5-yl, 2,5-dihydrothiazol-2-yl,2,5-dihydrothiazol-4-yl, 2,5-dihydrothiazol-5-yl,2,3-dihydrothiazol-2-yl, 2,3-dihydrothiazol-4-yl,2,3-dihydrothiazol-5-yl, 1,3-dioxol-2-yl, 1,3-dioxol-4-yl,1,3-dithiol-2-yl, 1,3-dithiol-4-yl, 1,3-oxathiol-2-yl,1,3-oxathiol-4-yl, 1,3-oxathiol-5-yl;

C-bound, 6-membered, partially unsaturated rings, such as2H-3,4-dihydropyran-6-yl, 2H-3,4-dihydropyran-5-yl,2H-3,4-dihydropyran-4-yl, 2H-3,4-dihydropyran-3-yl,2H-3,4-dihydropyran-2-yl, 2H-3,4-dihydrothiopyran-6-yl,2H-3,4-dihydrothiopyran-5-yl, 2H-3,4-dihydrothiopyran-4-yl,2H-3,4-dihydrothiopyran-3-yl, 2H-3,4-dihydrothiopyran-2-yl,1,2,3,4-tetrahydropyridin-6-yl, 1,2,3,4-tetrahydropyridin-5-yl,1,2,3,4-tetrahydropyridin-4-yl, 1,2,3,4-tetra-hydropyridin-3-yl,1,2,3,4-tetrahydropyridin-2-yl, 2H-5,6-dihydropyran-2-yl,2H-5,6-dihydropyran-3-yl, 2H-5,6-dihydropyran-4-yl,2H-5,6-dihydropyran-5-yl, 2H-5,6-dihydropyran-6-yl,2H-5,6-dihydrothiopyran-2-yl, 2H-5,6-dihydrothiopyran-3-yl,2H-5,6-dihydrothiopyran-4-yl, 2H-5,6-dihydrothiopyran-5-yl,2H-5,6-dihydrothiopyran-6-yl, 1,2,5,6-tetrahydropyridin-2-yl,1,2,5,6-tetrahydropyridin-3-yl, 1,2,5,6-tetrahydropyridin-4-yl,1,2,5,6-tetrahydropyridin-5-yl, 1,2,5,6-tetrahydropyridin-6-yl,2,3,4,5-tetrahydropyridin-2-yl, 2,3,4,5-tetrahydropyridin-3-yl,2,3,4,5-tetrahydropyridin-4-yl, 2,3,4,5-tetrahydropyridin-5-yl,2,3,4,5-tetrahydropyridin-6-yl, 4H-pyran-2-yl, 4H-pyran-3-yl-,4H-pyran-4-yl, 4H-thiopyran-2-yl, 4H-thiopyran-3-yl, 4H-thiopyran-4-yl,1,4-dihydropyridin-2-yl, 1,4-dihydropyridin-3-yl,1,4-dihydropyridin-4-yl, 2H-pyran-2-yl, 2H-pyran-3-yl, 2H-pyran-4-yl,2H-pyran-5-yl, 2H-pyran-6-yl, 2H-thiopyran-2-yl, 2H-thiopyran-3-yl,2H-thiopyran-4-yl, 2H-thiopyran-5-yl, 2H-thiopyran-6-yl,1,2-dihydropyridin-2-yl, 1,2-dihydro-pyridin-3-yl,1,2-dihydropyridin-4-yl, 1,2-dihydropyridin-5-yl,1,2-dihydro-pyridin-6-yl, 3,4-dihydropyridin-2-yl,3,4-dihydropyridin-3-yl, 3,4-dihydro-pyridin-4-yl,3,4-dihydropyridin-5-yl, 3,4-dihydropyridin-6-yl,2,5-dihydropyridin-2-yl, 2,5-dihydropyridin-3-yl,2,5-dihydropyridin-4-yl, 2,5-dihydropyridin-5-yl,2,5-dihydropyridin-6-yl, 2,3-dihydropyridin-2-yl,2,3-dihydropyridin-3-yl, 2,3-dihydropyridin-4-yl,2,3-dihydropyridin-5-yl, 2,3-dihydropyridin-6-yl,2H-5,6-dihydro-1,2-oxazin-3-yl, 2H-5,6-dihydro-1,2-oxazin-4-yl,2H-5,6-dihydro-1,2-oxazin-5-yl, 2H-5,6-dihydro-1,2-oxazin-6-yl,2H-5,6-dihydro-1,2-thiazin-3-yl, 2H-5,6-dihydro-1,2-thiazin-4-yl,2H-5,6-dihydro-1,2-thiazin-5-yl, 2H-5,6-dihydro-1,2-thiazin-6-yl,4H-5,6-dihydro-1,2-oxazin-3-yl, 4H-5,6-dihydro-1,2-oxazin-4-yl,4H-5,6-dihydro-1,2-oxazin-5-yl, 4H-5,6-dihydro-1,2-oxazin-6-yl,4H-5,6-dihydro-1,2-thiazin-3-yl, 4H-5,6-dihydro-1,2-thiazin-4-yl,4H-5,6-dihydro-1,2-thiazin-5-yl, 4H-5,6-dihydro-1,2-thiazin-6-yl,2H-3,6-dihydro-1,2-oxazin-3-yl, 2H-3,6-dihydro-1,2-oxazin-4-yl,2H-3,6-dihydro-1,2-oxazin-5-yl, 2H-3,6-dihydro-1,2-oxazin-6-yl,2H-3,6-dihydro-1,2-thiazin-3-yl, 2H-3,6-dihydro-1,2-thiazin-4-yl,2H-3,6-dihydro-1,2-thiazin-5-yl, 2H-3,6-dihydro-1,2-thiazin-6-yl,2H-3,4-dihydro-1,2-oxazin-3-yl, 2H-3,4-dihydro-1,2-oxazin-4-yl,2H-3,4-dihydro-1,2-oxazin-5-yl, 2H-3,4-dihydro-1,2-oxazin-6-yl,2H-3,4-dihydro-1,2-thiazin-3-yl, 2H-3,4-dihydro-1,2-thiazin-4-yl,2H-3,4-dihydro-1,2-thiazin-5-yl, 2H-3,4-dihydro-1,2-thiazin-6-yl,2,3,4,5-tetrahydropyridazin-3-yl, 2,3,4,5-tetrahydropyridazin-4-yl,2,3,4,5-tetrahydropyridazin-5-yl, 2,3,4,5-tetrahydropyridazin-6-yl,3,4,5,6-tetrahydropyridazin-3-yl, 3,4,5,6-tetrahydropyridazin-4-yl,1,2,5,6-tetrahydropyridazin-3-yl, 1,2,5,6-tetrahydropyridazin-4-yl,1,2,5,6-tetra-hydropyridazin-5-yl, 1,2,5,6-tetrahydropyridazin-6-yl,1,2,3,6-tetrahydro-pyridazin-3-yl, 1,2,3,6-tetrahydropyridazin-4-yl,4H-5,6-dihydro-1,3-oxazin-2-yl, 4H-5,6-dihydro-1,3-oxazin-4-yl,4H-5,6-dihydro-1,3-oxazin-5-yl, 4H-5,6-dihydro-1,3-oxazin-6-yl,4H-5,6-dihydro-1,3-thiazin-2-yl, 4H-5,6-dihydro-1,3-thiazin-4-yl,4H-5,6-dihydro-1,3-thiazin-5-yl, 4H-5,6-dihydro-1,3-thiazin-6-yl,3,4,5-6-tetrahydropyrimidin-2-yl, 3,4,5,6-tetrahydropyrimidin-4-yl,3,4,5,6-tetrahydropyrimidin-5-yl, 3,4,5,6-tetrahydropyrimidin-6-yl,1,2,3,4-tetrahydropyrazin-2-yl, 1,2,3,4-tetrahydropyrazin-5-yl,1,2,3,4-tetrahydro-pyrimidin-2-yl, 1,2,3,4-tetrahydropyrimidin-4-yl,1,2,3,4-tetrahydropyrimidin-5-yl, 1,2,3,4-tetrahydropyrimidin-6-yl,2,3-dihydro-1,4-thiazin-2-yl, 2,3-dihydro-1,4-thiazin-3-yl,2,3-dihydro-1,4-thiazin-5-yl, 2,3-dihydro-1,4-thiazin-6-yl,2H-1,3-oxazin-2-yl, 2H-1,3-oxazin-4-yl, 2H-1,3-oxazin-5-yl,2H-1,3-oxazin-6-yl, 2H-1,3-thiazin-2-yl, 2H-1,3-thiazin-4-yl,2H-1,3-thiazin-5-yl, 2H-1,3-thiazin-6-yl, 4H-1,3-oxazin-2-yl,4H-1,3-oxazin-4-yl, 4H-1,3-oxazin-5-yl, 4H-1,3-oxazin-6-yl,4H-1,3-thiazin-2-yl, 4H-1,3-thiazin-4-yl, 4H-1,3-thiazin-5-yl,4H-1,3-thiazin-6-yl, 6H-1,3-oxazin-2-yl, 6H-1,3-oxazin-4-yl,6H-1,3-oxazin-5-yl, 6H-1,3-oxazin-6-yl, 6H-1,3-thiazin-2-yl,6H-1,3-oxazin-4-yl, 6H-1,3-oxazin-5-yl, 6H-1,3-thiazin-6-yl,2H-1,4-oxazin-2-yl, 2H-1,4-oxazin-3-yl, 2H-1,4-oxazin-5-yl,2H-1,4-oxazin-6-yl, 2H-1,4-thiazin-2-yl, 2H-1,4-thiazin-3-yl,2H-1,4-thiazin-5-yl, 2H-1,4-thiazin-6-yl, 4H-1,4-oxazin-2-yl,4H-1,4-oxazin-3-yl, 4H-1,4-thiazin-2-yl, 4H-1,4-thiazin-3-yl,1,4-dihydropyridazin-3-yl, 1,4-dihydropyridazin-4-yl,1,4-dihydropyridazin-5-yl, 1,4-dihydropyridazin-6-yl,1,4-dihydropyrazin-2-yl, 1,2-dihydropyrazin-2-yl,1,2-dihydropyrazin-3-yl, 1,2-dihydropyrazin-5-yl,1,2-dihydropyrazin-6-yl, 1,4-dihydropyrimidin-2-yl,1,4-dihydropyrimidin-4-yl, 1,4-dihydropyrimidin-5-yl,1,4-dihydropyrimidin-6-yl, 3,4-dihydropyrimidin-2-yl,3,4-dihydropyrimidin-4-yl, 3,4-dihydropyrimidin-5-yl or3,4-dihydropyrimidin-6-yl;

N-bound, 5-membered, partially unsaturated rings, such as2,3-dihydro-1H-pyrrol-1-yl, 2,5-dihydro-1H-pyrrol-1-yl,4,5-dihydro-1H-pyrazol-1-yl, 2,5-dihydro-1H-pyrazol-1-yl,2,3-dihydro-1H-pyrazol-1-yl, 2,5-dihydroisoxazol-2-yl,2,3-dihydroisoxazol-2-yl, 2,5-dihydroisothiazol-2-yl,2,3-dihydroisoxazol-2-yl, 4,5-dihydro-1H-imidazol-1-yl,2,5-dihydro-1H-imidazol-1-yl, 2,3-dihydro-1H-imidazol-1-yl,2,3-dihydrooxazol-3-yl, 2,3-dihydrothiazol-3-yl;

N-bound, 6-membered, partially unsaturated rings, such as1,2,3,4-tetrahydropyridin-1-yl, 1,2,5,6-tetrahydropyridin-1-yl,1,4-dihydro-pyridin-1-yl, 1,2-dihydropyridin-1-yl,2H-5,6-dihydro-1,2-oxazin-2-yl, 2H-5,6-dihydro-1,2-thiazin-2-yl,2H-3,6-dihydro-1,2-oxazin-2-yl, 2H-3,6-dihydro-1,2-thiazin-2-yl,2H-3,4-dihydro-1,2-oxazin-2-yl, 2H-3,4-dihydro-1,2-thiazin-2-yl,2,3,4,5-tetrahydropyridazin-2-yl, 1,2,5,6-tetrahydropyridazin-1-yl,1,2,5,6-tetrahydropyridazin-2-yl, 1,2,3,6-tetrahydropyridazin-1-yl,3,4,5,6-tetrahydropyrimidin-3-yl, 1,2,3,4-tetrahydropyrazin-1-yl,1,2,3,4-tetrahydropyrimidin-1-yl, 1,2,3,4-tetrahydropyrimidin-3-yl,2,3-dihdro-1,4-thiazin-4-yl, 2H-1,2-oxazin-2-yl, 2H-1,2-thiazin-2-yl,4H-1,4-oxazin-4-yl, 4H-1,4-thiazin-4-yl, 1,4-dihydropyridazin-1-yl,1,4-dihydropyrazin-1-yl, 1,2-dihydropyrazin-1-yl,1,4-dihydropyrimidin-1-yl or 3,4-dihydropyrimidin-3-yl;

C-bound, 5-membered, heteroaromatic rings, such as 2-furyl, 3-furyl,2-thienyl, 3-thienyl, pyrrol-2-yl, pyrrol-3-yl, pyrazol-3-yl,pyrazol-4-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl,isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, imidazol-2-yl,imidazol-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, thiazol-2-yl,thiazol-4-yl, thiazol-5-yl, 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl,1,2,4-oxadiazol-3-yl, 1,2,4,-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl,1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl, 1,2,4-thiadiazol-3-yl,1,2,4-thiadiazol-5-yl, 1,3,4-thiadiazolyl-2-yl, 1,2,3-triazol-4-yl,1,2,4-triazol-3-yl, tetrazol-5-yl;

C-bound, 6-membered, heteroaromatic rings, such as pyridin-2-yl,pyridin-3-yl, pyridin-4-yl (4-pyridyl), pyridazin-3-yl, pyridazin-4-yl,pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrazin-2-yl,1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl,1,2,4-triazin-6-yl, 1,2,4,5-tetrazin-3-yl;

N-bound, 5-membered, heteroaromatic rings, such as pyrrol-1-yl,pyrazol-1-yl, imidazol-1-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl,tetrazol-1-yl.

Heterocyclyl also includes bicyclic heterocycles, which comprise one ofthe described 5- or 6-membered heterocyclic rings and a furtheranellated, saturated or unsaturated or aromatic carbocycle, such as abenzene, cyclohexane, cyclohexene or cyclohexadiene ring, or a furtheranellated 5- or 6-membered heterocyclic ring, this heterocyclic ringbeing saturated or unsaturated or aromatic. These include quinolinyl,isoquinolinyl, indolyl, indolizinyl, isoindolyl, indazolyl, benzofuryl,benzthienyl, benzo[b]thiazolyl, benzoxazolyl, benzthiazolyl andbenzimidazolyl. Examples of 5- or 6-membered heteroaromatic compoundscomprising an anellated cycloalkenyl ring include dihydroindolyl,dihydroindolizinyl, dihydroisoindolyl, dihydroquinolinyl,dihydroisoquinolinyl, chromenyl and chromanyl.

C₃-C₁₂-Heteroarylene is a heteroaryl diradical. Examples includepyrid-2,5-ylene and pyrid-2,4-ylene.

With respect to the compounds' capability of inhibiting glycinetransporter 1, the variables A, R, R¹, W, A¹, Q, Y, A², X¹, R², R³, Y¹,R^(4a), R^(4b), X², X³, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴,R¹⁵, R¹⁶, R¹⁷, n preferably have the following meanings which, whentaken alone or in combination, represent particular embodiments of thecompounds of the formula (I), (II) or any other formula disclosedherein.

In said formula (I) or (II), there may be one or more than onesubstituent R, R² and/or R³. More particularly, there may be up to 3substituents R², and up to 6 substituents R³. Preferably there is onesubstituent R and 1, 2 or 3 substituents R². Formula (I) may thus bedepicted as follows:

wherein a is 1, 2 or 3, b is 1, 2, 3, 4, 5 or 6 and c is 1. If there ismore than one radical R², these may be the same or different radicals.If there is more than one radical R³, these may be the same or differentradicals.

A is a 5- or 6-membered ring which includes two carbon atoms from thecyclopentane, cyclohexane or cycloheptane moiety to which A is fused. Amay be a homocyclic or heterocyclic ring. The ring may be saturated,unsaturated non-aromatic or aromatic. According to a particularembodiment, A is a benzene ring. As a heterocyclic ring, A may include1, 2 or 3 heteroatoms as ring member atoms, which are selected,independently of each other from N, S and O. Preferred heterocyclicrings comprise 1 nitrogen atom as ring member atom and optionally 1 or 2further heteroatoms as ring members, which are selected, independentlyof each other from O, S and N. Likewise preferred heterocyclic ringscomprise 1 heteroatom as ring member atom, which is selected from O, Sand N, and optionally 1 or 2 further nitrogen atoms as ring memberatoms. According to a particular embodiment, A is a heterocyclic ringselected from the group consisting of the following 5- or 6-memberedheterocyclic rings:

In said formulae, hydrogen atoms are not depicted. This is meant toillustrate that the free valency of a carbon or nitrogen atom may beeither bound to a hydrogen atom, to R or to R². Accordingly, R and R²may be C- or N-bound at any position of ring A.

The skilled person will appreciate that some of the rings depicted abovemay be represented with a different structure, e.g. with hydrogen atomshaving other positions than those shown above, for instance as given inthe following structures:

Preferably, A is a heterocyclic ring selected from the group consistingof the following 5- or 6-membered heterocyclic rings:

According to a further particular embodiment, A is a heterocyclic ringselected from the group consisting of the following 5- or 6-memberedheterocyclic rings:

According to a preferred embodiment, A is a heterocyclic ring selectedfrom the group consisting of the following 5- or 6-membered heterocyclicrings:

If ring A is a 5-membered heterocyclic ring it is preferred that R isbound to G¹ or G², in particular G²:

In said formula, G¹, G² and G³ independently are —CH═, —CH₂—, —N═, —NH—,S or O, at least one of G¹, G² and G³ is —CH═ or —CH₂—, the dotted linerepresents a single or a double bond and R³, Y¹, R^(4a), R^(4b), X², X³,R⁵, n are as defined herein.

If ring A is 6-membered heterocyclic ring it is preferred that R isbound to G¹ or G², in particular G²:

In said formula, G¹, G², G³ and G⁴ independently are —CH═, —CH₂—, —N═,—NH—, S or O, at least one of G¹, G², G³ and G⁴ is —CH═ or —CH₂—, thedotted line represents a single or a double bond and R³, Y¹, R^(4a),R^(4b), X², X³, R⁵, n are as defined herein.

Heterocyclic compounds having the following partial structures arepreferred:

Heterocyclic compounds having the following partial structures areparticularly preferred:

In said formulae, R and R² are as defined herein. If there is more thanone radical R², these may be the same or different radicals.

According to a particular embodiment, the partial structures depictedabove are fused with a cyclohexane moiety (i.e., n is 1). The sameapplies to the preferred and particular embodiments disclosed for ringA.

According to one embodiment, R is cyano.

Preferably, R is R¹—W-A¹-Q-Y-A²-X¹- and A, R¹, W, A¹, Q, Y, A², X¹, R²,R³, Y¹, R^(4a), R^(4b), X², X³, R⁵, n are as defined herein.

R¹ is hydrogen, C₁-C₆-alkyl (e.g. methyl, ethyl, n-propyl, isopropyl,n-butyl, sec-butyl or n-pentyl), C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl (e.g.cyclopropylmethyl, cyclopentylmethyl or cyclohexylmethyl), halogenatedC₁-C₆-alkyl (e.g. 3-fluoroprop-1-yl, 3-chloroprop-1-yl or3,3,3-trifluoroprop-1-yl), tri-(C₁-C₄-alkyl)-silyl-C₁-C₄-alkyl (e.g.trimethylsilylethyl), hydroxy-C₁-C₄-alkyl C₁-C₆-alkoxy-C₁-C₄-alkyl (e.g.ethoxyethyl), amino-C₁-C₄-alkyl, C₁-C₆ alkylamino C₁-C₄ alkyl, di-C₁-C₆alkylamino C₁-C₄ alkyl, C₁-C₆-alkylcarbonylamino-C₁-C₄-alkyl,C₁-C₆-alkyloxycarbonylamino-C₁-C₆-alkyl,C₁-C₆-alkylaminocarbonylamino-C₁-C₄-alkyl,di-C₁-C₆-alkylaminocarbonylamino-C₁-C₄-alkyl,C₁-C₆-alkylsulfonylamino-C₁-C₄-alkyl, (optionally substitutedC₆-C₁₂-aryl-C₁-C₆-alkyl)amino-C₁-C₄-alkyl, optionally substitutedC₆-C₁₂-aryl-C₁-C₄-alkyl, optionally substitutedC₃-C₁₂-heterocyclyl-C₁-C₄-alkyl, C₃-C₁₂-cycloalkyl (e.g. cyclopropyl orcyclobutyl), C₁-C₆-alkylcarbonyl, C₁-C₆-alkoxycarbonyl, halogenatedC₁-C₆-alkoxycarbonyl, C₆-C₁₂-aryloxycarbonyl, aminocarbonyl,C₁-C₆-alkylaminocarbonyl, (halogenated C₁-C₄-alkyl)aminocarbonyl,C₆-C₁₂-arylaminocarbonyl, C₂-C₆-alkenyl (e.g. prop-1,2-en-1-yl),C₂-C₆-alkynyl, optionally substituted C₆-C₁₂-aryl (e.g. phenyl,2-methylphenyl), hydroxy, C₁-C₆-alkoxy (e.g. tert-butyloxy), halogenatedC₁-C₆-alkoxy, C₁-C₆-hydroxyalkoxy, C₁-C₆-alkoxy-C₁-C₄-alkoxy,amino-C₁-C₄-alkoxy, C₁-C₆-alkylamino-C₁-C₄-alkoxy,di-C₁-C₆-alkylamino-C₁-C₄-alkoxy, C₁-C₆-alkylcarbonylamino-C₁-C₄-alkoxy,C₆-C₁₂-arylcarbonylamino-C₁-C₄-alkoxy,C₁-C₆-alkoxycarbonylamino-C₁-C₄-alkoxy, C₆-C₁₂-aryl-C₁-C₄-alkoxy,C₁-C₆-alkylsulfonylamino-C₁-C₄-alkoxy, (halogenatedC₁-C₆-alkyl)sulfonylamino-C₁-C₄-alkoxy,C₆-C₁₂-arylsulfonylamino-C₁-C₄-alkoxy,(C₆-C₁₂-aryl-C₁-C₆-alkyl)sulfonylamino-C₁-C₄-alkoxy,C₃-C₁₂-heterocyclylsulfonylamino-C₁-C₄-alkoxy,C₃-C₁₂-heterocyclyl-C₁-C₄-alkoxy, C₆-C₁₂-aryloxy,C₃-C₁₂-heterocyclyloxy, C₁-C₆-alkylthio, halogenated C₁-C₆-alkylthio,C₁-C₆-alkylamino, (halogenated C₁-C₆-alkyl)amino, di-C₁-C₆-alkylamino(e.g. dimethylamino), di-(halogenated C₁-C₆-alkyl)amino,C₁-C₆-alkylcarbonylamino, (halogenated C₁-C₆-alkyl)carbonylamino,C₆-C₁₂-arylcarbonylamino, C₁-C₆-alkylsulfonylamino, (halogenatedC₁-C₆-alkyl)sulfonylamino, C₆-C₁₂-arylsulfonylamino or optionallysubstituted C₃-C₁₂-heterocyclyl (e.g. 3-pyridyl, 2-thienyl,4-methyl-2-thienyl, 5-methyl-2-thienyl, 5-chloro-2-thienyl,2,5-dimethyl-3-thienyl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl,1-ethyl-1,2-diazol-4-yl, 1-difluormethyl-1,2-diazol-4-yl,2-methyl-1,3-diazol-4-yl, 1-methyl-1,3-diazol-4-yl,2-methyl-1,3-thiazol-5-yl, 2,4-dimethyl-1,3-thiazol-5-yl,3-pyrrolidinyl, 1-methyl-pyrrol-3-yl, 2-pyridyl,1-methyl-1,2-diazol-3-yl, 1-methyl-3-trifluoromethyl-1,2-diazol-4-yl,1,2-dimethyl-1,3-diazol-4-yl, 5-methylisoxazol-3-yl or1-methyl-1,2,4-triazol-3-yl).

Preferably, R¹ is C₁-C₆-alkyl (e.g. methyl, ethyl, n-propyl, isopropyl,sec-butyl, n-butyl or n-pentyl), C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl (e.g.cyclopropylmethyl, cyclopentylmethyl or cyclohexylmethyl), halogenatedC₁-C₆-alkyl (e.g. 3-fluoroprop-1-yl, 3-chloroprop-1-yl or3,3,3-trifluoroprop-1-yl), tri-(C₁-C₄-alkyl)-silyl-C₁-C₄-alkyl (e.g.trimethylsilylethyl), C₁-C₆-alkoxy-C₁-C₄-alkyl (e.g. ethoxyethyl),amino-C₁-C₄-alkyl, C₁-C₆-alkylamino C₁-C₄ alkyl, di-C₁-C₆-alkylaminoC₁-C₄ alkyl, C₁-C₆-alkyloxycarbonylamino-C₁-C₄-alkyl,C₁-C₆-alkylaminocarbonylamino-C₁-C₄-alkyl, C₆-C₁₂-aryl-C₁-C₄-alkyl,C₃-C₁₂-cycloalkyl (e.g. cyclopropyl or cyclobutyl), C₂-C₆-alkenyl (e.g.prop-1,2-en-1-yl), optionally substituted C₆-C₁₂-aryl (e.g. phenyl),hydroxy, C₁-C₆-alkylamino, (halogenated C₁-C₆-alkyl)amino,di-C₁-C₆-alkylamino or optionally substituted C₃-C₁₂-heterocyclyl (e.g.3-pyridyl, 2-thienyl, 4-methyl-2-thienyl, 5-methyl-2-thienyl,5-chloro-2-thienyl, 2,5-dimethyl-3-thienyl, 1,2-diazol-4-yl,1-methyl-1,2-diazol-4-yl, 1-ethyl-1,2-diazol-4-yl,1-difluormethyl-1,2-diazol-4-yl, 2-methyl-1,3-diazol-4-yl,1-methyl-1,3-diazol-4-yl, 2-methyl-1,3-thiazol-5-yl,2,4-dimethyl-1,3-thiazol-5-yl or 3-pyrrolidinyl).

In particular, R¹ is C₁-C₆-alkyl (e.g. n-propyl),C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl (e.g. cyclopropylmethyl),C₃-C₁₂-cycloalkyl (e.g. cyclobutyl), or optionally substitutedC₃-C₁₂-heterocyclyl, (e.g. 3-pyridyl, 1-methyl-1,2-diazol-4-yl,1-methyl-1,3-diazol-4-yl, 3-oxetanyl, 1-methylpyrrol-3-yl).

In connection with R¹, substituted C₆-C₁₂-aryl in particular includesC₆-C₁₂-aryl, such as phenyl or naphthyl, substituted with 1, 2 or 3substituents selected from the group consisting of halogen, C₁-C₄-alkyl,C₁-C₄-haloalkyl, cyano, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, amino,C₁-C₄-alkylamino, C₁-C₄-dialkylamino, morpholino and piperidinyl. Thesame applies to substituted C₆-C₁₂-aryl in substitutedC₆-C₁₂-aryl-C₁-C₄-alkyl.

In connection with R¹, substituted C₃-C₁₂-heterocyclyl in particularincludes C₃-C₁₂-heterocyclyl, such as pyridyl, thienyl, diazolyl,quinolinyl, piperidinyl, piperazinyl or morpholinyl, pyrrolyl,isoxazolyl and triazolyl being further examples of suchC₃-C₁₂-heterocyclyl, substituted with 1, 2 or 3 substituents selectedfrom the group consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl,C₁-C₄-alkoxycarbonyl, cyano, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy,C₁-C₄-alkylsulfonyl, amino, C₁-C₄-alkylamino, C₁-C₄-dialkylamino,C₆-C₁₂-arylamino and C₃-C₁₂-heterocyclyl (e.g., morpholino orpiperidinyl). The same applies to substituted C₃-C₁₂-heteroaryl insubstituted C₃-C₁₂-heteroaryl-C₁-C₄-alkyl.

According to one embodiment, W is —NR⁸— and Y is a bond. According to analternative embodiment, W is a bond and Y is —NR⁹—. According to afurther alternative embodiment, W is a bond and Y is a bond, especiallyif R¹ is a nitrogen-bound radical, e.g. nitrogen-bound heterocyclyl suchas piperazinyl or morpholinyl.

According to one embodiment, Q is —S(O)₂—. According to an alternativeembodiment, Q is —C(O)—.

According to a particular embodiment, —W-A¹-Q-Y— is —W-A¹-S(O)₂—NR⁹—,—NR⁸—S(O)₂—, -A¹-S(O)₂— or —S(O)₂—. According to a further particularembodiment, —W-A¹-Q-Y— is —W-A¹-CO—NR⁹— or —NR⁸—CO—.

A¹ is optionally substituted C₁-C₄-alkylene or a bond. In connectionwith A¹, substituted C₁-C₄-alkylene in particular includesC₁-C₄-alkylene substituted with 1, 2 or 3 substituents selected from thegroup consisting of halogen, C₁-C₄-alkyl and cyano. Preferably, A¹ is abond. If A¹ is C₁-C₄-alkylene, W is preferably —NR^(B)—.

A² is optionally substituted C₁-C₄-alkylene (e.g. 1,2-ethylene or1,3-propylene), C₁-C₄-alkylene-CO—, —CO—C₁-C₄-alkylene,C₁-C₄-alkylene-O—C₁-C₄-alkylene, C₁-C₄-alkylene-NR¹⁰—C₁-C₄-alkylene,optionally substituted C₆-C₁₂-arylene, optionally substitutedC₆-C₁₂-heteroarylene or a bond. Additionally, A² may be optionallysubstituted C₂-C₄-alkenylene or optionally substituted C₂-C₄-alkynylene.Preferably, A² is optionally substituted C₁-C₄-alkylene (e.g.1,2-ethylene or 1,3-propylene). More preferably, A² is C₁-C₄-alkylene(e.g. 1,2-ethylene). Alternatively, it is preferred that A² isoptionally substituted C₆-C₁₂-arylene, in particular C₆-C₁₂-aryleneselected from the group consisting of phen-1,4-ylene and phen-1,3-ylene,or optionally substituted C₆-C₁₂-heteroarylene, in particularC₆-C₁₂-heteroarylene selected from the group consisting ofpyrid-2,5-ylene and pyrid-2,4-ylene. If A² is a bond, X¹ is preferablyoptionally substituted C₁-C₄-alkylene. Alternatively, if A² is a bond,X¹ is in particular optionally substituted C₂-C₄-alkenylene oroptionally substituted C₂-C₄-alkynylene.

In connection with A², substituted C₁-C₄-alkylene in particular includesC₁-C₄-alkylene substituted with 1, 2 or 3 substituents selected from thegroup consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl and cyano.

In connection with A², substituted C₂-C₄-alkenylene or substitutedC₂-C₄-alkynylene in particular includes C₂-C₄-alkenylene orC₂-C₄-alkynylene substituted with 1, 2 or 3 substituents selected fromthe group consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl and cyano.

In connection with A², substituted C₆-C₁₂-arylene in particular includesC₆-C₁₂-arylene substituted with 1, 2 or 3 substituents selected from thegroup consisting of C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxycarbonyl,cyano, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylsulfonyl, amino,C₁-C₄-alkylamino, C₁-C₄ dialkylamino, C₆-C₁₂-arylamino andC₃-C₁₂-heterocyclyl (e.g., morpholino or piperidinyl).

In connection with A², substituted C₆-C₁₂-heteroarylene in particularincludes C₆-C₁₂-heteroarylene substituted with 1, 2 or 3 substituentsselected from the group consisting of C₁-C₄ alkyl, C₁-C₄ haloalkyl,C₁-C₄-alkoxycarbonyl, cyano, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy,C₁-C₄-alkylsulfonyl, amino, C₁-C₄-alkylamino, C₁-C₄ dialkylamino,C₆-C₁₂-arylamino and C₃-C₁₂-heterocyclyl (e.g., morpholino orpiperidinyl).

X¹ is —O—, —NR¹¹—, —S— or optionally substituted C₁-C₄-alkylene (e.g.—CH₂—, 1,2-ethylene and 1,3-propylene). In connection with X¹,substituted C₁-C₄-alkylene in particular includes C₁-C₄-alkylenesubstituted with 1, 2 or 3 substituents selected from the groupconsisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl and cyano.Additionally, X¹ may be optionally substituted C₂-C₄-alkenylen oroptionally substituted C₂-C₄-alkynylene (e.g. propynylene). Inconnection with X¹, substituted C₂-C₄-alkenylene or substitutedC₂-C₄-alkynylene in particular includes C₂-C₄-alkenylene orC₂-C₄-alkynylene substituted with 1, 2 or 3 substituents selected fromthe group consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl and cyano.Preferably, X¹ is —O—, —NR¹¹, —S—. More preferably, X¹ is —O—.Alternatively, it is preferred if X¹ is optionally substitutedC₁-C₄-alkylene (e.g. —CH₂— or 1,2-ethylene).

According to a particular embodiment, A² is a bond and X¹ is optionallysubstituted C₁-C₄-alkylene, optionally substituted C₂-C₄-alkenylene oroptionally substituted C₂-C₄-alkynylene.

According to a particular embodiment, R¹—W-A¹-Q-Y-A²-X¹— isR¹—S(O)₂—NH-A²-X¹—, R¹—NH—S(O)₂-A²-X¹—, R¹—C(O)—NH-A²-X¹- orR¹—NH—C(O)-A²-X¹-.

According to a particular embodiment, the structural element —Y-A²-X¹-comprises at least 2, 3 or 4 atoms in the main chain. According tofurther particular embodiments the structural element —Y-A²-X¹- has upto 4, 5 or 6 atoms in the main chain, such as 2 to 6, 2 to 5 or 2 to 4atoms in the main chain, especially 2, 3 or 4 atoms in the main chain.

According to a further particular embodiment, —Y-A²-X¹— is—C₁-C₄-alkylene-O— or —NR⁹—C₁-C₄-alkylene-O—, with —Y-A²-X¹- preferablyhaving 2 to 6, 3 to 5 and especially 4 atoms in the main chain.Particular examples of —Y-A²-X¹- include —(CH₂)₃—O— and —NR⁹—(CH₂)₂—O—.In this particular embodiment, R⁹ is as defined herein and preferably R⁹is hydrogen, C₁-C₆-alkyl (e.g. methyl or ethyl) or C₃-C₁₂-cycloalkyl(e.g. cyclopropyl), or R⁹ is C₁-C₄-alkylene that is bound to a carbonatom in A² which is C₁-C₄-alkylene.

According to a further particular embodiment, —Y-A²-X¹- is—NR⁹—C₁-C₄-alkylene- (e.g. —NH—CH₂—, —NH—(CH₂)₂— or —NH—(CH₂)₃—), with—Y-A²-X¹- preferably having 2 to 6, 2 to 5, 2 to 4 and especially 2, 3or 4 atoms in the main chain. In this particular embodiment, R⁹ is asdefined herein and preferably R⁹ is hydrogen, C₁-C₆-alkyl (e.g. methylor ethyl) or C₃-C₁₂-cycloalkyl (e.g. cyclopropyl); or R⁹ isC₁-C₄-alkylene that is bound to a carbon atom in X¹ which isC₁-C₄-alkylene.

According to a further particular embodiment, —Y-A²-X¹- is—NR⁹—C₂-C₄-alkenylene- or —NR⁹—C₂-C₄-alkynylene- (e.g. —NH—CH₂—C≡C—),with —Y-A²-X¹- preferably having 2 to 6, 3 to 5 and especially 4 atomsin the main chain. In this particular embodiment, R⁹ is as definedherein and preferably is R⁹ is hydrogen, C₁-C₆-alkyl (e.g. methyl orethyl) or C₃-C₁₂-cycloalkyl (e.g. cyclopropyl or cyclobutyl). If A is aheterocyclic ring, this embodiment of —Y-A²-X¹- is particularlysuitable.

According to a further particular embodiment, —Y-A²-X¹- is—C₁-C₄-alkylene- (e.g. —(CH₂)₂—), with —Y-A²-X¹- preferably having 2 to6, 2 to 5, 2 to 4 and especially 2 atoms in the main chain. If A is aheterocyclic ring, this embodiment of —Y-A²-X¹- is particularlysuitable.

According to a further particular embodiment, the structural motif—Y-A²-X¹ as disclosed herein is bound to Q being —S(O)₂— or —C(O)—.Particular examples for this embodiment include heterocyclic compoundsof the invention wherein R is R¹—S(O)₂—Y-A²-X¹ or R¹—C(O)—Y-A²-X¹.

The radical R and in particular the radical R¹—W-A¹-Q-Y-A²-X¹— X¹- may,in principle, be bound to the 5-, 6-, 7- or 8-position of the skeletonof the compounds of the invention:

In said formulae, R¹, W, A¹, Q, Y, A², X¹, R², R³, Y¹, R^(4a), R^(4b),X², X³, R⁵, n are as defined herein.

Further particular examples include compounds of the above formulaewherein the radical R¹—W-A¹-Q-Y-A²-X¹— is replaced by the radical —CN.

Compounds of the invention having the radical R¹—W-A¹-Q-Y-A²-X¹- (or theradical —CN) in the 5-, 6-, 7-position are preferred.

Particularly preferred are compounds of the invention having the radicalR¹—W-A¹-Q-Y-A²-X¹— (or the radical —CN) in the 7-position.

In addition to the radical R¹—W-A¹-Q-Y-A²-X¹— (or the radical —CN), thecompounds of the invention may have one or more than one furthersubstituent bound to the ring A. In these positions, the skeleton of thecompounds of the invention may thus be substituted with one or more thanone radical R². If there is more than one radical R², these may be thesame or different radicals. In particular, in 5-, 6-, 7- and/or8-position, the skeleton of the compounds of the invention may besubstituted with one or more than one radical R². The compounds of theinvention may therefore be represented by one of the following formulae:

or by corresponding formulae wherein the radical R¹—W-A¹-Q-Y-A²-X¹- isreplaced by the radical —CN,wherein R^(2a), R^(2b), R^(2c), R^(2d) independently have one of themeanings given for R², and R¹, W, A¹, Q, Y, A², X¹, R², R³, Y¹, R^(4a),R^(4b), X², X³, R⁵, n are as defined herein.

R² is hydrogen, halogen (e.g. fluorine), C₁-C₆-alkyl, halogenatedC₁-C₄-alkyl, hydroxy-C₁-C₄-alkyl, —CN, C₂-C₆-alkenyl, C₂-C₆-alkynyl,optionally substituted C₆-C₁₂-aryl, hydroxy, C₁-C₆-alkoxy, halogenatedC₁-C₆-alkoxy, C₁-C₆-alkoxycarbonyl, C₂-C₆-alkenyloxy,C₆-C₁₂-aryl-C₁-C₄-alkoxy, C₁-C₆-alkylcarbonyloxy, C₁-C₆-alkylthio,C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, aminosulfonyl, amino,C₁-C₆-alkylamino, C₂-C₆-alkenylamino, nitro or optionally substitutedC₃-C₁₂-heterocyclyl, or two radicals R² together with the ring atoms towhich they are bound form a 5- or 6 membered ring.

An optionally substituted 5- or 6-membered ring that is formed by tworadicals R² together with the ring atoms of A to which they are boundis, for instance, a benzene ring.

In connection with R², substituted C₆-C₁₂-aryl in particular includesC₆-C₁₂-aryl, such as phenyl, substituted with 1, 2 or 3 substituentsselected from the group consisting of halogen and C₁-C₄-alkyl, C₁-C₄haloalkyl, cyano, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy.

In connection with R², substituted C₃-C₁₂-heterocyclyl in particularincludes C₃-C₁₂-heterocyclyl, such as morpholinyl, pyrrolidinyl andpiperidinyl, substituted with 1, 2 or 3 substituents selected from thegroup consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, cyano,C₁-C₄-alkoxy and C₁-C₄-haloalkoxy.

Preferably, R² is hydrogen, halogen (e.g. fluorine) or C₁-C₆-alkoxy. Inparticular, R² is hydrogen or halogen (e.g. fluorine).

According to a particular embodiment, the compounds of the inventionhave one of the following formulae:

or by corresponding formulae wherein the radical R¹—W-A¹-Q-Y-A²-X¹- isreplaced by the radical —CN,wherein W, A¹, O, Y, A², X¹, R², R³, Y¹, R^(4a), R^(4b), X², X³, R⁵, nare as defined herein.

In 1-, 2-, 3- and/or 4-position, the compounds of the invention may besubstituted with one or more than one radical R³. If there is more thanone radical R³, these may be the same or different radicals. Thecompounds of the invention may therefore be represented by the followingformula:

wherein R^(3a), R^(3b), R^(3c), R^(3d), R^(3e), R^(3f) independentlyhave one of the meanings given for R³, and A, R, R², R³, Y¹, R^(4a),R^(4b), X², X³, R⁵, n are as defined herein.

According to a particular embodiment, the compounds of the inventionhave one of the following formulae:

wherein R^(3a), R^(3b), R^(3f) independently have the meaning of R³ andA, R, R², R³, Y¹, R^(4a), R^(4b), X², X³, R⁵, n are as defined herein.

R³ is hydrogen, halogen, C₁-C₆-alkyl, C₁-C₆-alkoxy, or two radicals R³together with the carbon atom to which they are attached form a carbonylgroup.

Preferably, R³ is hydrogen or C₁-C₆-alkyl. In particular, R³ ishydrogen.

Y¹ is optionally substituted C₁-C₄-alkylene (e.g. methylene or1,2-ethylene). In connection with Y¹, substituted C₁-C₄-alkylene inparticular includes C₁-C₄-alkylene substituted with 1, 2 or 3substituents selected from the group consisting of halogen, C₁-C₄-alkyl,C₁-C₄-haloalkyl, C₃-C₁₂-cycloalkyl and cyano. In particular, Y¹ isC₁-C₄-alkylene (e.g. methylene or 1,2-ethylene).

R^(4a) is hydrogen, C₁-C₆-alkyl (e.g. methyl, ethyl, n-propyl orisopropyl), C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl (e.g. cyclopropylmethyl),halogenated C₁-C₄-alkyl (e.g. 2-fluoroethyl or 2,2,2-trifluoroethyl),hydroxy-C₁-C₄-alkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl, amino-C₁-C₄-alkyl, CH₂CN,C₆-C₁₂-aryl-C₁-C₄-alkyl (e.g. benzyl), C₃-C₁₂-cycloalkyl (e.g.cyclopropyl), —CHO, C₁-C₄-alkylcarbonyl (e.g. methylcarbonyl,ethylcarbonyl or isopropylcarbonyl), (halogenated C₁-C₄-alkyl)carbonyl(e.g. fluoromethylcarbonyl, difluoromethylcarbonyl,trifluoromethylcarbonyl, 1,1,1-trifluoroeth-2-ylcarbonyl or1,1,1-trifluoroprop-3-ylcarbonyl), C₆-C₁₂-arylcarbonyl (e.g.phenylcarbonyl), C₁-C₄-alkoxycarbonyl (e.g. ethoxycarbonyl ortertbutyloxycarbonyl), C₆-C₁₂-aryloxycarbonyl (e.g. phenoxycarbonyl),C₁-C₆-alkylaminocarbonyl, C₂-C₆-alkenyl, —C(═NH)NH₂, —C(═NH)NHCN,C₁-C₆-alkylsulfonyl, C₆-C₁₂-arylsulfonyl, amino, —NO orC₃-C₁₂-heterocyclyl (e.g. 3-oxetanyl).

Preferably, R^(4a) is hydrogen, C₁-C₆-alkyl (e.g. methyl, ethyl,n-propyl or isopropyl), C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl (e.g.cyclopropylmethyl), halogenated C₁-C₄-alkyl (e.g. 2-fluoroethyl or2,2,2-trifluoroethyl), amino-C₁-C₄-alkyl, CH₂CN,C₆-C₁₂-aryl-C₁-C₄-alkyl(e.g. benzyl), C₃-C₁₂-cycloalkyl (e.g. cyclopropyl), C₁-C₁-alkylcarbonyl(e.g. methylcarbonyl or isopropylcarbonyl), (halogenatedC₁-C₄-alkyl)carbonyl (e.g. fluoromethylcarbonyl, difluoromethylcarbonylor trifluoromethylcarbonyl), C₆-C₁₂-arylcarbonyl (e.g. phenylcarbonyl),C₁-C₄-alkoxycarbonyl (e.g. ethoxycarbonyl or tert-butyloxycarbonyl),C₆-C₁₂-aryloxycarbonyl (e.g. phenoxycarbonyl), —C(═NH)NH₂, —C(═NH)NHCN,C₁-C₆-alkylsulfonyl, amino, —NO or C₃-C₁₂-heterocyclyl (e.g.3-oxetanyl).

In particular, R^(4a) is hydrogen, C₁-C₆-alkyl (e.g. methyl),C₃-C₁₂-cycloalkyl (e.g. cyclopropyl), or C₃-C₁₂-heterocyclyl (e.g.3-oxetanyl).

Alternatively, R^(4a) is optionally substituted C₁-C₄-alkylene (e.g.methylene or 1,2-ethylene) that is bound to a carbon atom in Y¹. Inconnection with R^(4a), substituted C₁-C₄-alkylene in particularincludes C₁-C₄-alkylene substituted with 1, 2 or 3 substituents selectedfrom the group consisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, andcyano, with hydroxy and C₁-C₄-alkoxy being further substituents. Inparticular, R^(4a) is C₁-C₄-alkylene (e.g. methylene or 1,2-ethylene)that is bound to a carbon atom in Y¹ with Y¹ being optionallysubstituted C₁-C₄-alkylene (e.g. 1,2-ethylene or 1,3-propylene) so thatR^(4a) and at least part of Y¹ together with the nitrogen atom to whichR^(4a) and Y¹ are bound form an N-containing heterocyclic ring having,in particular, 4, 5 or 6 ring member atoms (including the nitrogenatom). An alkylaminotetralin or indane derivative having such a ring maybe represented by the following partial structure:

wherein A, R, R², R³, R^(4b), X², X³, R⁵, n are as defined herein, s is0, 1 or 2, and t is 0, 1, 2, or 3. Particular combinations of s and tinclude s=1, t=1; s=0, t=1; s=1, t=2; and s=0, t=2.

R^(4b) is hydrogen, C₁-C₆-alkyl (e.g. methyl, ethyl), halogenatedC₁-C₄-alkyl, hydroxy-C₁-C₄-alkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl,amino-C₁-C₄-alkyl, CH₂CN, —CHO, C₁-C₄-alkylcarbonyl, (halogenatedC₁-C₄-alkyl)carbonyl, C₆-C₁₂-arylcarbonyl, C₁-C₄-alkoxycarbonyl,C₆-C₁₂-aryloxycarbonyl, C₁-C₆-alkylaminocarbonyl, C₂-C₆-alkenyl,—C(═NH)NH₂, —C(═NH)NHCN, C₁-C₆-alkylsulfonyl, C₆-C₁₂-arylsulfonyl,amino, —NO or C₃-C₁₂-heterocyclyl.

Preferably, R^(4b) is hydrogen, C₁-C₆-alkyl (e.g. methyl). Inparticular, R^(4b) is hydrogen.

Alternatively, R^(4a), R^(4b) together are optionally substitutedC₁-C₆-alkylene (e.g. 1,4-butylene, 1,3-propylene, 2-fluoro-but-1,4-yleneor 1-oxo-but-1,4-ylene), wherein one —CH₂— of C₁-C₆-alkylene may bereplaced by an oxygen atom (e.g. —CH₂—CH₂—O—CH₂—CH₂—) or —NR¹⁶.

In connection with R^(4a) and R^(4b), substituted C₁-C₆-alkylene inparticular includes C₁-C₆-alkylene substituted with 1, 2 or 3substituents selected from the group consisting of halogen (e.g. fluoroor chloro), C₁-C₄-alkyl, cyano, hydroxy and C₁-C₄-alkoxy.

X² is —O—, —NR⁶—, —S—, >CR^(12a)R^(12b) or a bond. Preferably, X² is>CR^(12a)R^(12b).

X³ is —O—, —S—, >CR^(13a)R^(13b) or a bond. Preferably, X³ is a bond.

Thus, it is preferred if X² is >CR^(12a)R^(12b) and X³ is a bond.

R^(12a) is hydrogen, optionally substituted C₁-C₆-alkyl,C₁-C₆-alkylamino-C₁-C₄-alkyl, di-C₁-C₆-alkylamino-C₁-C₄-alkyl,C₃-C₁₂-heterocyclyl-C₁-C₆-alkyl, optionally substituted C₆-C₁₂-aryl orhydroxy. Preferably, R^(12a) is hydrogen or C₁-C₆-alkyl.

R^(13a) is hydrogen, optionally substituted C₁-C₆-alkyl,C₁-C₆-alkylamino-C₁-C₄-alkyl, di-C₁-C₆-alkylamino-C₁-C₄-alkyl,C₃-C₁₂-heterocyclyl-C₁-C₆-alkyl, optionally substituted C₆-C₁₂-aryl orhydroxy. Preferably, R^(13a) is hydrogen or C₁-C₆-alkyl.

In connection with R^(12a) and R^(13a), substituted C₁-C₆-alkyl inparticular includes C₁-C₆-alkyl substituted with 1, 2 or 3 substituentsselected from the group consisting of halogen, hydroxy, C₁-C₄-alkoxy andamino.

In connection with R^(12a) and R^(13a), substituted C₆-C₁₂-aryl inparticular includes C₆-C₁₂-aryl, such as phenyl, substituted with 1, 2or 3 substituents selected from the group consisting of C₁-C₄-alkyl,C₁-C₄-haloalkyl, cyano, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy.

R^(12b) is hydrogen or C₁-C₆-alkyl. According to a particularembodiment, R^(12b) is hydrogen.

R^(13b) is hydrogen or C₁-C₆-alkyl. According to a particularembodiment, R^(13b) is hydrogen.

Alternatively, R^(12a) and R^(12b), or R^(13a) and R^(13b), together aretogether are carbonyl or, preferably, optionally substitutedC₁-C₄-alkylene (e.g. 1,3-propylene), wherein one —CH₂— of C₁-C₄-alkylenemay be replaced by an oxygen atom or —NR¹⁴—.

In connection with R^(12a) and R^(12b), or R^(13a) and R^(13b),substituted C₁-C₄-alkylene in particular includes C₁-C₄-alkylenesubstituted with 1, 2 or 3 substituents selected from the groupconsisting of halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, cyano, C₁-C₄-alkoxyand C₁-C₄-haloalkoxy.

According to a particular embodiment, R^(12a) is C₁-C₆-alkyl and R^(12b)is hydrogen or C₁-C₆-alkyl, or R^(13a) is C₁-C₆-alkyl and R^(13b) ishydrogen or C₁-C₆-alkyl.

According to a further particular embodiment, R^(12a) is hydrogen andR^(12b) is hydrogen, or R^(13a) is hydrogen and R^(13b) is hydrogen.

According to a further particular embodiment, R^(12a) and R^(12b)together are optionally substituted 1,3-propylene, or R^(13a) andR^(13b) together are optionally substituted 1,3-propylene.

R⁵ is optionally substituted C₆-C₁₂-aryl (e.g. phenyl, 2-fluorophenyl,2-chlorophenyl, 3-fluorophenyl, 3-chlorophenyl; 3-cyanophenyl,3-methylphenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl,4-fluorophenyl, 4-chlorophenyl, 4-methoxyphenyl, 3,4-difluorophenyl,3,5-difluorophenyl, 3-fluoro-5-chlorophenyl, 3-chloro-4-fluorophenyl,2,4-dichlorophenyl or 3,4-dichlorophenyl), optionally substitutedC₃-C₁₂-cycloalkyl (e.g. cyclohexyl) or optionally substitutedC₃-C₁₂-heterocyclyl.

In connection with R⁵, substituted C₃-C₁₂-cycloalkyl in particularincludes C₃-C₁₂-cycloalkyl, such as cyclopropyl or cyclohexyl,substituted with 1, 2 or 3 substituents selected from the groupconsisting of halogen, optionally substituted C₁-C₆-alkyl, halogenatedC₁-C₆-alkyl, CN, hydroxy, C₁-C₆-alkoxy, halogenated C₁-C₆-alkoxy, amino,C₁-C₆-alkylamino, di-C₁-C₆-alkylamino and C₃-C₁₂-heterocyclyl.

In connection with R⁵, substituted C₆-C₁₂-aryl in particular includesC₆-C₁₂-aryl, such as phenyl, substituted with 1, 2 or 3 substituentsselected from the group consisting of halogen (e.g. F, Cl, Br),optionally substituted C₁-C₆-alkyl (e.g. methyl), halogenatedC₁-C₆-alkyl (e.g. trifluoromethyl), CN, hydroxy, C₁-C₆-alkoxy (e.g.methoxy), halogenated C₁-C₆-alkoxy, amino, C₁-C₆-alkylamino,di-C₁-C₆-alkylamino and C₃-C₁₂-heterocyclyl.

In connection with R⁵, substituted C₃-C₁₂-heterocyclyl in particularincludes C₃-C₁₂-heterocyclyl substituted with 1, 2 or 3 substituentsselected from the group consisting of halogen, optionally substitutedC₁-C₆-alkyl, halogenated C₁-C₆-alkyl, CN, hydroxy, C₁-C₆-alkoxy,halogenated C₁-C₆-alkoxy, amino, C₁-C₆-alkylamino, di-C₁-C₆-alkylaminoand C₃-C₁₂-heterocyclyl.

In connection with R⁵, C₃-C₁₂-heterocyclyl in particular isC₃-C₁₂-heteroaryl.

Preferably, R⁵ is optionally substituted C₆-C₁₂-aryl, in particular asin the compounds of the formula:

wherein A, R, R², R³, Y¹, R^(4a), R^(4b), X², X³, n are as definedherein, and R^(17a), R^(17b), R^(17c), R^(17d), R^(17e) independentlyare hydrogen, halogen (e.g. F, Cl or Br), optionally substitutedC₁-C₆-alkyl (e.g. methyl), halogenated C₁-C₆-alkyl (e.g.trifluoromethyl), CN, hydroxy, C₁-C₆-alkoxy (e.g. methoxy), amino,C₁-C₆-alkylamino, di-C₁-C₆-alkylamino or C₃-C₁₂-heterocyclyl.

It is also preferred if R⁵ is optionally substituted C₆-C₁₂-heteroaryl,in particular as in the aminoindane derivatives of the formula:

wherein A, R, R², R³, Y¹, R^(4a), R^(4b), X², X³, n are as definedherein, and R^(17b), R^(17c), R^(17d), R^(17e) independently arehydrogen, halogen (e.g. F, Cl or Br), optionally substituted C₁-C₆-alkyl(e.g. methyl), halogenated C₁-C₆-alkyl (e.g. trifluoromethyl), CN,hydroxy, C₁-C₆-alkoxy (e.g. methoxy), amino, C₁-C₆-alkylamino,di-C₁-C₆-alkylamino or C₃-C₁₂-heterocyclyl.

According to a particular embodiment, the invention relates to compoundsof the formula:

wherein A, R, R², R³, Y¹, R^(4a), R^(4b), R⁵, n are as defined herein,R⁵ preferably being optionally substituted aryl and in particularoptionally substituted phenyl as disclosed herein.

In connection with R⁵ or R^(17a), R^(17b), R^(17c), R^(17d), R^(17e)substituted C₁-C₆-alkyl in particular includes C₁-C₆-alkyl, especiallyC₁-C₄-alkyl, substituted with 1, 2 or 3 substituents selected from thegroup consisting of hydroxy, C₁-C₆-alkoxy, amino, C₁-C₆-alkylamino,di-C₁-C₆-alkylamino and C₃-C₁₂-heterocyclyl (e.g. morpholinyl orpiperidinyl).

According to a particular embodiment, R^(17a), R^(17b), R^(17d), R^(17e)are hydrogen and R^(17c) is different from hydrogen(para-mono-substitution).

According to a further particular embodiment, R^(17a), R^(17c), R^(17d),R^(17e) are hydrogen and R^(17b) is different from hydrogen(meta-mono-substitution).

In connection with R^(17a), R^(17b), R^(17c), R^(17d), R^(17e),C₃-C₁₂-heterocyclyl in particular includes morpholinyl, imidazolyl andpyrazolyl.

R⁶ is hydrogen or C₁-C₆-alkyl. Preferably, R⁶ is hydrogen.

R⁷ is hydrogen or C₁-C₆-alkyl. Preferably, R⁷ is hydrogen.

R⁸ is hydrogen or C₁-C₆-alkyl. Preferably, R⁸ is hydrogen.

R⁹ is hydrogen, C₁-C₆-alkyl (e.g. methyl or ethyl), C₃-C₁₂-cycloalkyl(e.g. cyclopropyl), amino-C₁-C₆-alkyl, optionally substitutedC₆-C₁₂-aryl-C₁-C₄-alkyl or C₃-C₁₂-heterocyclyl (e.g. 3-azetidinyl).Preferably, R⁹ is hydrogen or C₁-C₆-alkyl (e.g. methyl or ethyl).

According to a particular embodiment, R⁹ and R¹ together areC₁-C₄-alkylene (e.g. 1, 3-1,2-ethylene or propylene) so as that R⁹ andR¹ together with the atom in Q to which R¹ is bound and the nitrogenatom to which R⁹ is bound form an heterocyclic ring having, inparticular, 4, 5 or 6 ring member atoms (including the nitrogen atom andQ). With W and A¹ both being a bond, such a ring may be represented bythe following partial structure:

wherein Q, A², X¹, are as defined herein (e.g. S(O)₂) and n is 0, 1, 2,3 or 4.

According to a further particular embodiment, R⁹ is C₁-C₄-alkylene (e.g.methylene or 1,3-propylene) that is bound to a carbon atom in A² and A²is C₁-C₄-alkylene so that R⁹ and at least part of A² together with thenitrogen atom to which R⁹ is bound form an N-containing heterocyclicring having, in particular, 4, 5, 6 or 7 ring member atoms (includingthe nitrogen atom). Such a ring may be represented by the followingpartial structure:

wherein W, A¹, Q and X¹ are as defined herein, p is 1 or 2, r is 0, 1 or2 and q is 0, 1 or 2. In this particular embodiment, X¹ preferably is—O—. Particular combinations of p, r and q include p=1, r=0, q=1; andp=1, r=0, q=0. Alternatively, p is 0, r is 3 and q is 1, with X¹preferably being —O—.

According to a further particular embodiment, R⁹ is C₁-C₄-alkylene (e.g.methylene or 1,3-propylene) that is bound to a carbon atom in X¹ and X¹is C₁-C₄-alkylene (e.g. 1,2-ethylene) so that R⁹ and at least part of X¹together with the nitrogen atom to which R⁹ is bound form anN-containing heterocyclic ring having, in particular, 4, 5, 6 or 7 ringmember atoms (including the nitrogen atom). With A² being a bond, such aring may be represented by the following partial structure:

wherein R¹, W, A¹ and Q are as defined herein, p is 1 or 2, r is 0, 1 or2 and q is 0, 1 or 2. Particular combinations of p, r and q include p=1,r=0, q=0.

R¹⁰ is hydrogen, C₁-C₆-alkyl or C₁-C₆-alkylsulfonyl. Preferably, R¹⁰ ishydrogen.

R¹¹ is hydrogen or C₁-C₆-alkyl. Preferably, R¹¹ is hydrogen.

Alternatively, R⁹, R¹¹ together are C₁-C₄-alkylene (e.g. ethylene).

R¹⁴ is hydrogen or C₁-C₆-alkyl. Preferably, R¹⁴ is hydrogen.

R¹⁵ is hydrogen or C₁-C₆-alkyl. Preferably, R¹⁵ is hydrogen.

R¹⁶ is hydrogen or C₁-C₆-alkyl. Preferably, R¹⁶ is hydrogen.

Particular embodiments of compounds of the invention result if

-   A is a benzene ring;-   R is R¹—W-A¹-Q-Y-A²-X¹-;-   R¹ is C₁-C₆-alkyl (e.g. n-propyl), C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl    (e.g. cyclopropylmethyl), C₃-C₁₂-cycloalkyl (e.g. cyclobutyl), or    optionally substituted C₃-C₁₂-heterocyclyl (e.g. 3-pyridyl,    1-methyl-1,2-diazol-4-yl, 1-methyl-1,3-diazol-4-yl, 3-oxetanyl,    1-methylpyrrol-3-yl);-   W is a bond;-   A¹ is a bond;-   Q is —S(O)₂—;-   Y is —NR⁹— or a bond;-   A² is C₁-C₄-alkylene (e.g. 1,2-ethylene) or a bond;-   X¹ is —O— or optionally substituted C₁-C₄-alkylene (e.g. methylene,    1,2-ethylene);-   R² is hydrogen or halogen (e.g. fluorine);-   R³ is hydrogen;-   Y¹ is optionally substituted C₁-C₄-alkylene (e.g. methylene,    1,2-ethylene);-   R^(4a) is hydrogen, C₁-C₆-alkyl (e.g. methyl), C₃-C₁₂-cycloalkyl    (e.g. cyclopropyl) or optionally substituted C₃-C₁₂-heterocyclyl    (e.g. 3-oxetanyl); or-   R^(4a) is C₁-C₄-alkylene (e.g. methylene, 1,2-ethylene) that is    bound to a carbon atom in Y¹ and Y¹ is optionally substituted    C₁-C₄-alkylene (e.g. 1,2-ethylene, 1,3-propylene);-   R^(4b) is hydrogen; or-   R^(4a), R^(4b)    -   together are C₁-C₆-alkylene (e.g. 1,3-propylene, 1,4-butylene),        wherein one —CH₂— of C₁-C₆-alkylene may be replaced by an oxygen        atom (e.g. —CH₂—CH₂—O—CH₂—CH₂—);-   X² is >CR^(12a)R^(12b);-   X³ is a bond;-   R⁵ is optionally substituted phenyl (e.g. phenyl, 2-fluorophenyl,    2-chlorophenyl, 3-fluorophenyl, 3-chlorophenyl,    3-trifluoromethylphenyl);-   n is 0 or 1;-   R⁹ is hydrogen, or-   R⁹ is C₁-C₄-alkylene (e.g. methylene) that is bound to a carbon atom    in X¹ and X¹ is C₁-C₄-alkylene (e.g. 1,2-ethylene);-   R^(12a) is hydrogen;-   R^(12b) is hydrogen; or-   R^(12a), R^(12b)    -   together are C₁-C₄-alkylene (e.g. 1,3-propylene).

Further particular compounds of the present invention are the individualderivatives (in particular tetraline and indane derivatives) of theformula (Id) as listed in the following tables 1 to 24 andphysiologically tolerated salts thereof:

Table 1

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is hydrogen, R³ is asdefined herein and in particular represents hydrogen, R¹⁷ is hydrogenand the combination of R¹, —Y-A²-X¹—, >CR^(12a)R^(12b), R^(4a), R^(4b)for a compound in each case corresponds to one line of Table A (A-1 toA-480).

Table 2

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is hydrogen, R³ is asdefined herein and in particular represents hydrogen, R¹⁷ is 3-F and thecombination of R¹, —Y-A²-X¹—, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 3

Compounds of the formula (Id) wherein —Y¹— is as defined herein and inparticular represents —CH₂— or —(—CH₂)₂—, R² is hydrogen, R³ is asdefined herein and in particular represents hydrogen, R¹⁷ is 3-Cl andthe combination of R¹, —Y-A²-X¹—, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 4

Compounds of the formula (Id) wherein —Y¹— is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is hydrogen, R³ is asdefined herein and in particular represents hydrogen, R¹⁷ is 3-CF₃ andthe combination of R¹, —Y-A²-X¹—, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 5

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is hydrogen, R³ is asdefined herein and in particular represents hydrogen, R¹⁷ is 2-F and thecombination of R¹, —Y-A²-X¹—, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 6

Compounds of the formula (Id) wherein —Y¹— is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is hydrogen, R³ is asdefined herein and in particular represents hydrogen, R¹⁷ is 2-Cl andthe combination of R¹, —Y-A²-X¹—, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 7

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 5-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is hydrogen and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 8

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 5-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 3-F and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 9

Compounds of the formula (Id) wherein —Y¹— is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 5-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 3-Cl and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 10

Compounds of the formula (Id) wherein —Y¹— is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 5-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 3-CF₃ and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 11

Compounds of the formula (Id) wherein —Y¹— is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 5-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 2-F and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 12

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 5-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 2-Cl and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 13

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 6-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is hydrogen and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 14

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 6-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 3-F and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 15

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 6-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 3-Cl and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 16

Compounds of the formula (Id) wherein —Y¹— is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 6-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 3-CF₃ and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 17

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 6-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 2-F and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 18

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or (CH₂)₂—, R² is 6-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 2-Cl and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for a fora compound in each case corresponds to one line of Table A (A-1 toA-480).

Table 19

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 8-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is hydrogen and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 20

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 8-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 3-F and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 21

Compounds of the formula (Id) wherein —Y¹— is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 8-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 3-Cl and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 22

Compounds of the formula (Id) wherein —Y¹— is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 8-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 3-CF₃ and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 23

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 8-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 2-F and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

Table 24

Compounds of the formula (Id) wherein —Y¹- is as defined herein and inparticular represents —CH₂— or —(CH₂)₂—, R² is 8-F, R³ is as definedherein and in particular represents hydrogen, R¹⁷ is 2-Cl and thecombination of R¹, —Y-A²-X¹-, >CR^(12a)R^(12b), R^(4a), R^(4b) for acompound in each case corresponds to one line of Table A (A-1 to A-480).

R¹ —Y—A²—X¹— >CR^(12a)R^(12b) R^(4a), R^(4b) A-1.

—NH—(CH₂)₂—O— —CH₂— —CH₃, H A-2.

—NH—(CH₂)₂—O— —CH₂— —CH₃, H A-3.

—NH—(CH₂)₂—O— —CH₂— —CH₃, H A-4.

—NH—(CH₂)₂—O— —CH₂— —CH₃, H A-5.

—NH—(CH₂)₂—O— —CH₂— —CH₃, H A-6.

—NH—(CH₂)₂—O— —CH₂— —CH₃, H A-7.

—NH—(CH₂)₂—O— —CH₂— —CH₃, H A-8.

—NH—(CH₂)₂—O— —CH₂— —CH₃, H A-9.

—NH—(CH₂)₂— —CH₂— —CH₃, H A-10.

—NH—(CH₂)₂— —CH₂— —CH₃, H A-11.

—NH—(CH₂)₂— —CH₂— —CH₃, H A-12.

—NH—(CH₂)₂— —CH₂— —CH₃, H A-13.

—NH—(CH₂)₂— —CH₂— —CH₃, H A-14.

—NH—(CH₂)₂— —CH₂— —CH₃, H A-15.

—NH—(CH₂)₂— —CH₂— —CH₃, H A-16.

—NH—(CH₂)₂— —CH₂— —CH₃, H A-17.

—NH—CH₂— —CH₂— —CH₃, H A-18.

—NH—CH₂— —CH₂— —CH₃, H A-19.

—NH—CH₂— —CH₂— —CH₃, H A-20.

—NH—CH₂— —CH₂— —CH₃, H A-21.

—NH—CH₂— —CH₂— —CH₃, H A-22.

—NH—CH₂— —CH₂— —CH₃, H A-23.

—NH—CH₂— —CH₂— —CH₃, H A-24.

—NH—CH₂— —CH₂— —CH₃, H A-25.

—CH₂— —CH₃, H A-26.

—CH₂— —CH₃, H A-27.

—CH₂— —CH₃, H A-28.

—CH₂— —CH₃, H A-29.

—CH₂— —CH₃, H A-30.

—CH₂— —CH₃, H A-31.

—CH₂— —CH₃, H A-32.

—CH₂— —CH₃, H A-33.

—(CH₂)₂— —CH₂— —CH₃, H A-34.

—(CH₂)₂— —CH₂— —CH₃, H A-35.

—(CH₂)₂— —CH₂— —CH₃, H A-36.

—(CH₂)₂— —CH₂— —CH₃, H A-37.

—(CH₂)₂— —CH₂— —CH₃, H A-38.

—(CH₂)₂— —CH₂— —CH₃, H A-39.

—(CH₂)₂— —CH₂— —CH₃, H A-40.

—(CH₂)₂— —CH₂— —CH₃, H A-41.

—NH—(CH₂)₂—O—

—CH₃, H A-42.

—NH—(CH₂)₂—O—

—CH₃, H A-43.

—NH—(CH₂)₂—O—

—CH₃, H A-44.

—NH—(CH₂)₂—O—

—CH₃, H A-45.

—NH—(CH₂)₂—O—

—CH₃, H A-46.

—NH—(CH₂)₂—O—

—CH₃, H A-47.

—NH—(CH₂)₂—O—

—CH₃, H A-48.

—NH—(CH₂)₂—O—

—CH₃, H A-49.

—NH—(CH₂)₂—

—CH₃, H A-50.

—NH—(CH₂)₂—

—CH₃, H A-51.

—NH—(CH₂)₂—

—CH₃, H A-52.

—NH—(CH₂)₂—

—CH₃, H A-53.

—NH—(CH₂)₂—

—CH₃, H A-54.

—NH—(CH₂)₂—

—CH₃, H A-55.

—NH—(CH₂)₂—

—CH₃, H A-56.

—NH—(CH₂)₂—

—CH₃, H A-57.

—NH—CH₂—

—CH₃, H A-58.

—NH—CH₂—

—CH₃, H A-59.

—NH—CH₂—

—CH₃, H A-60.

—NH—CH₂—

—CH₃, H A-61.

—NH—CH₂—

—CH₃, H A-62.

—NH—CH₂—

—CH₃, H A-63.

—NH—CH₂—

—CH₃, H A-64.

—NH—CH₂—

—CH₃, H A-65.

—CH₃, H A-66.

—CH₃, H A-67.

—CH₃, H A-68.

—CH₃, H A-69.

—CH₃, H A-70.

—CH₃, H A-71.

—CH₃, H A-72.

—CH₃, H A-73.

—(CH₂)₂—

—CH₃, H A-74.

—(CH₂)₂—

—CH₃, H A-75.

—(CH₂)₂—

—CH₃, H A-76.

—(CH₂)₂—

—CH₃, H A-77.

—(CH₂)₂—

—CH₃, H A-78.

—(CH₂)₂—

—CH₃, H A-79.

—(CH₂)₂—

—CH₃, H A-80.

—(CH₂)₂—

—CH₃, H A-81.

—NH—(CH₂)₂—O— —CH₂—

A-82.

—NH—(CH₂)₂—O— —CH₂—

A-83.

—NH—(CH₂)₂—O— —CH₂—

A-84.

—NH—(CH₂)₂—O— —CH₂—

A-85.

—NH—(CH₂)₂—O— —CH₂—

A-86.

—NH—(CH₂)₂—O— —CH₂—

A-87.

—NH—(CH₂)₂—O— —CH₂—

A-88.

—NH—(CH₂)₂—O— —CH₂—

A-89.

—NH—(CH₂)₂— —CH₂—

A-90.

—NH—(CH₂)₂— —CH₂—

A-91.

—NH—(CH₂)₂— —CH₂—

A-92.

—NH—(CH₂)₂— —CH₂—

A-93.

—NH—(CH₂)₂— —CH₂—

A-94.

—NH—(CH₂)₂— —CH₂—

A-95.

—NH—(CH₂)₂— —CH₂—

A-96.

—NH—(CH₂)₂— —CH₂—

A-97.

—NH—CH₂— —CH₂—

A-98.

—NH—CH₂— —CH₂—

A-99.

—NH—CH₂— —CH₂—

A-100.

—NH—CH₂— —CH₂—

A-101.

—NH—CH₂— —CH₂—

A-102.

—NH—CH₂— —CH₂—

A-103.

—NH—CH₂— —CH₂—

A-104.

—NH—CH₂— —CH₂—

A-105.

—CH₂—

A-106.

—CH₂—

A-107.

—CH₂—

A-108.

—CH₂—

A-109.

—CH₂—

A-110.

—CH₂—

A-111.

—CH₂—

A-112.

—CH₂—

A-113.

—(CH₂)₂— —CH₂—

A-114.

—(CH₂)₂— —CH₂—

A-115.

—(CH₂)₂— —CH₂—

A-116.

—(CH₂)₂— —CH₂—

A-117.

—(CH₂)₂— —CH₂—

A-118.

—(CH₂)₂— —CH₂—

A-119.

—(CH₂)₂— —CH₂—

A-120.

—(CH₂)₂— —CH₂—

A-121.

—NH—(CH₂)₂—O—

A-122.

—NH—(CH₂)₂—O—

A-123.

—NH—(CH₂)₂—O—

A-124.

—NH—(CH₂)₂—O—

A-125.

—NH—(CH₂)₂—O—

A-126.

—NH—(CH₂)₂—O—

A-127.

—NH—(CH₂)₂—O—

A-128.

—NH—(CH₂)₂—O—

A-129.

—NH—(CH₂)₂—

A-130.

—NH—(CH₂)₂—

A-131.

—NH—(CH₂)₂—

A-132.

—NH—(CH₂)₂—

A-133.

—NH—(CH₂)₂—

A-134.

—NH—(CH₂)₂—

A-135.

—NH—(CH₂)₂—

A-136.

—NH—(CH₂)₂—

A-137.

—NH—CH₂—

A-138.

—NH—CH₂—

A-139.

—NH—CH₂—

A-140.

—NH—CH₂—

A-141.

—NH—CH₂—

A-142.

—NH—CH₂—

A-143.

—NH—CH₂—

A-144.

—NH—CH₂—

A-145.

A-146.

A-147.

A-148.

A-149.

A-150.

A-151.

A-152.

A-153.

—(CH₂)₂—

A-154.

—(CH₂)₂—

A-155.

—(CH₂)₂—

A-156.

—(CH₂)₂—

A-157.

—(CH₂)₂—

A-158.

—(CH₂)₂—

A-159.

—(CH₂)₂—

A-160.

—(CH₂)₂—

A-161.

—NH—(CH₂)₂—O— —CH₂—

A-162.

—NH—(CH₂)₂—O— —CH₂—

A-163.

—NH—(CH₂)₂—O— —CH₂—

A-164.

—NH—(CH₂)₂—O— —CH₂—

A-165.

—NH—(CH₂)₂—O— —CH₂—

A-166.

—NH—(CH₂)₂—O— —CH₂—

A-167.

—NH—(CH₂)₂—O— —CH₂—

A-168.

—NH—(CH₂)₂—O— —CH₂—

A-169.

—NH—(CH₂)₂— —CH₂—

A-170.

—NH—(CH₂)₂— —CH₂—

A-171.

—NH—(CH₂)₂— —CH₂—

A-172.

—NH—(CH₂)₂— —CH₂—

A-173.

—NH—(CH₂)₂— —CH₂—

A-174.

—NH—(CH₂)₂— —CH₂—

A-175.

—NH—(CH₂)₂— —CH₂—

A-176.

—NH—(CH₂)₂— —CH₂—

A-177.

—NH—CH₂— —CH₂—

A-178.

—NH—CH₂— —CH₂—

A-179.

—NH—CH₂— —CH₂—

A-180.

—NH—CH₂— —CH₂—

A-181.

—NH—CH₂— —CH₂—

A-182.

—NH—CH₂— —CH₂—

A-183.

—NH—CH₂— —CH₂—

A-184.

—NH—CH₂— —CH₂—

A-185.

—CH₂—

A-186.

—CH₂—

A-187.

—CH₂—

A-188.

—CH₂—

A-189.

—CH₂—

A-190.

—CH₂—

A-191.

—CH₂—

A-192.

—CH₂—

A-193.

—(CH₂)₂— —CH₂—

A-194.

—(CH₂)₂— —CH₂—

A-195.

—(CH₂)₂— —CH₂—

A-196.

—(CH₂)₂— —CH₂—

A-197.

—(CH₂)₂— —CH₂—

A-198.

—(CH₂)₂— —CH₂—

A-199.

—(CH₂)₂— —CH₂—

A-200.

—(CH₂)₂— —CH₂—

A-201.

—NH—(CH₂)₂—O—

A-202.

—NH—(CH₂)₂—O—

A-203.

—NH—(CH₂)₂—O—

A-204.

—NH—(CH₂)₂—O—

A-205.

—NH—(CH₂)₂—O—

A-206.

—NH—(CH₂)₂—O—

A-207.

—NH—(CH₂)₂—O—

A-208.

—NH—(CH₂)₂—O—

A-209.

—NH—(CH₂)₂—

A-210.

—NH—(CH₂)₂—

A-211.

—NH—(CH₂)₂—

A-212.

—NH—(CH₂)₂—

A-213.

—NH—(CH₂)₂—

A-214.

—NH—(CH₂)₂—

A-215.

—NH—(CH₂)₂—

A-216.

—NH—(CH₂)₂—

A-217.

—NH—CH₂—

A-218.

—NH—CH₂—

A-219.

—NH—CH₂—

A-220.

—NH—CH₂—

A-221.

—NH—CH₂—

A-222.

—NH—CH₂—

A-223.

—NH—CH₂—

A-224.

—NH—CH₂—

A-225.

A-226.

A-227.

A-228.

A-229.

A-230.

A-231.

A-232.

A-233.

—(CH₂)₂—

A-234.

—(CH₂)₂—

A-235.

—(CH₂)₂—

A-236.

—(CH₂)₂—

A-237.

—(CH₂)₂—

A-238.

—(CH₂)₂—

A-239.

—(CH₂)₂—

A-240.

—(CH₂)₂—

A-241.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₃— A-242.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₃— A-243.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₃— A-244.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₃— A-245.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₃— A-246.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₃— A-247.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₃— A-248.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₃— A-249.

—NH—(CH₂)₂— —CH₂— —(CH₂)₃— A-250.

—NH—(CH₂)₂— —CH₂— —(CH₂)₃— A-251.

—NH—(CH₂)₂— —CH₂— —(CH₂)₃— A-252.

—NH—(CH₂)₂— —CH₂— —(CH₂)₃— A-253.

—NH—(CH₂)₂— —CH₂— —(CH₂)₃— A-254.

—NH—(CH₂)₂— —CH₂— —(CH₂)₃— A-255.

—NH—(CH₂)₂— —CH₂— —(CH₂)₃— A-256.

—NH—(CH₂)₂— —CH₂— —(CH₂)₃— A-257.

—NH—CH₂— —CH₂— —(CH₂)₃— A-258.

—NH—CH₂— —CH₂— —(CH₂)₃— A-259.

—NH—CH₂— —CH₂— —(CH₂)₃— A-260.

—NH—CH₂— —CH₂— —(CH₂)₃— A-261.

—NH—CH₂— —CH₂— —(CH₂)₃— A-262.

—NH—CH₂— —CH₂— —(CH₂)₃— A-263.

—NH—CH₂— —CH₂— —(CH₂)₃— A-264.

—NH—CH₂— —CH₂— —(CH₂)₃— A-265.

—CH₂— —(CH₂)₃— A-266.

—CH₂— —(CH₂)₃— A-267.

—CH₂— —(CH₂)₃— A-268.

—CH₂— —(CH₂)₃— A-269.

—CH₂— —(CH₂)₃— A-270.

—CH₂— —(CH₂)₃— A-271.

—CH₂— —(CH₂)₃— A-272.

—CH₂— —(CH₂)₃— A-273.

—(CH₂)₂— —CH₂— —(CH₂)₃— A-274.

—(CH₂)₂— —CH₂— —(CH₂)₃— A-275.

—(CH₂)₂— —CH₂— —(CH₂)₃— A-276.

—(CH₂)₂— —CH₂— —(CH₂)₃— A-277.

—(CH₂)₂— —CH₂— —(CH₂)₃— A-278.

—(CH₂)₂— —CH₂— —(CH₂)₃— A-279.

—(CH₂)₂— —CH₂— —(CH₂)₃— A-280.

—(CH₂)₂— —CH₂— —(CH₂)₃— A-281.

—NH—(CH₂)₂—O—

—(CH₂)₃— A-282.

—NH—(CH₂)₂—O—

—(CH₂)₃— A-283.

—NH—(CH₂)₂—O—

—(CH₂)₃— A-284.

—NH—(CH₂)₂—O—

—(CH₂)₃— A-285.

—NH—(CH₂)₂—O—

—(CH₂)₃— A-286.

—NH—(CH₂)₂—O—

—(CH₂)₃— A-287.

—NH—(CH₂)₂—O—

—(CH₂)₃— A-288.

—NH—(CH₂)₂—O—

—(CH₂)₃— A-289.

—NH—(CH₂)₂—

—(CH₂)₃— A-290.

—NH—(CH₂)₂—

—(CH₂)₃— A-291.

—NH—(CH₂)₂—

—(CH₂)₃— A-292.

—NH—(CH₂)₂—

—(CH₂)₃— A-293.

—NH—(CH₂)₂—

—(CH₂)₃— A-294.

—NH—(CH₂)₂—

—(CH₂)₃— A-295.

—NH—(CH₂)₂—

—(CH₂)₃— A-296.

—NH—(CH₂)₂—

—(CH₂)₃— A-297.

—NH—CH₂—

—(CH₂)₃— A-298.

—NH—CH₂—

—(CH₂)₃— A-299.

—NH—CH₂—

—(CH₂)₃— A-300.

—NH—CH₂—

—(CH₂)₃— A-301.

—NH—CH₂—

—(CH₂)₃— A-302.

—NH—CH₂—

—(CH₂)₃— A-303.

—NH—CH₂—

—(CH₂)₃— A-304.

—NH—CH₂—

—(CH₂)₃— A-305.

—(CH₂)₃— A-306.

—(CH₂)₃— A-307.

—(CH₂)₃— A-308.

—(CH₂)₃— A-309.

—(CH₂)₃— A-310.

—(CH₂)₃— A-311.

—(CH₂)₃— A-312.

—(CH₂)₃— A-313.

—(CH₂)₂—

—(CH₂)₃— A-314.

—(CH₂)₂—

—(CH₂)₃— A-315.

—(CH₂)₂—

—(CH₂)₃— A-316.

—(CH₂)₂—

—(CH₂)₃— A-317.

—(CH₂)₂—

—(CH₂)₃— A-318.

—(CH₂)₂—

—(CH₂)₃— A-319.

—(CH₂)₂—

—(CH₂)₃— A-320.

—(CH₂)₂—

—(CH₂)₃— A-321.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₄— A-322.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₄— A-323.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₄— A-324.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₄— A-325.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₄— A-326.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₄— A-327.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₄— A-328.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₄— A-329.

—NH—(CH₂)₂— —CH₂— —(CH₂)₄— A-330.

—NH—(CH₂)₂— —CH₂— —(CH₂)₄— A-331.

—NH—(CH₂)₂— —CH₂— —(CH₂)₄— A-332.

—NH—(CH₂)₂— —CH₂— —(CH₂)₄— A-333.

—NH—(CH₂)₂— —CH₂— —(CH₂)₄— A-334.

—NH—(CH₂)₂— —CH₂— —(CH₂)₄— A-335.

—NH—(CH₂)₂— —CH₂— —(CH₂)₄— A-336.

—NH—(CH₂)₂— —CH₂— —(CH₂)₄— A-337.

—NH—CH₂— —CH₂— —(CH₂)₄— A-338.

—NH—CH₂— —CH₂— —(CH₂)₄— A-339.

—NH—CH₂— —CH₂— —(CH₂)₄— A-340.

—NH—CH₂— —CH₂— —(CH₂)₄— A-341.

—NH—CH₂— —CH₂— —(CH₂)₄— A-342.

—NH—CH₂— —CH₂— —(CH₂)₄— A-343.

—NH—CH₂— —CH₂— —(CH₂)₄— A-344.

—NH—CH₂— —CH₂— —(CH₂)₄— A-345.

—CH₂— —(CH₂)₄— A-346.

—CH₂— —(CH₂)₄— A-347.

—CH₂— —(CH₂)₄— A-348.

—CH₂— —(CH₂)₄— A-349.

—CH₂— —(CH₂)₄— A-350.

—CH₂— —(CH₂)₄— A-351.

—CH₂— —(CH₂)₄— A-352.

—CH₂— —(CH₂)₄— A-353.

—(CH₂)₂— —CH₂— —(CH₂)₄— A-354.

—(CH₂)₂— —CH₂— —(CH₂)₄— A-355.

—(CH₂)₂— —CH₂— —(CH₂)₄— A-356.

—(CH₂)₂— —CH₂— —(CH₂)₄— A-357.

—(CH₂)₂— —CH₂— —(CH₂)₄— A-358.

—(CH₂)₂— —CH₂— —(CH₂)₄— A-359.

—(CH₂)₂— —CH₂— —(CH₂)₄— A-360.

—(CH₂)₂— —CH₂— —(CH₂)₄— A-361.

—NH—(CH₂)₂—O—

—(CH₂)₄— A-362.

—NH—(CH₂)₂—O—

—(CH₂)₄— A-363.

—NH—(CH₂)₂—O—

—(CH₂)₄— A-364.

—NH—(CH₂)₂—O—

—(CH₂)₄— A-365.

—NH—(CH₂)₂—O—

—(CH₂)₄— A-366.

—NH—(CH₂)₂—O—

—(CH₂)₄— A-367.

—NH—(CH₂)₂—O—

—(CH₂)₄— A-368.

—NH—(CH₂)₂—O—

—(CH₂)₄— A-369.

—NH—(CH₂)₂—

—(CH₂)₄— A-370.

—NH—(CH₂)₂—

—(CH₂)₄— A-371.

—NH—(CH₂)₂—

—(CH₂)₄— A-372.

—NH—(CH₂)₂—

—(CH₂)₄— A-373.

—NH—(CH₂)₂—

—(CH₂)₄— A-374.

—NH—(CH₂)₂—

—(CH₂)₄— A-375.

—NH—(CH₂)₂—

—(CH₂)₄— A-376.

—NH—(CH₂)₂—

—(CH₂)₄— A-377.

—NH—CH₂—

—(CH₂)₄— A-378.

—NH—CH₂—

—(CH₂)₄— A-379.

—NH—CH₂—

—(CH₂)₄— A-380.

—NH—CH₂—

—(CH₂)₄— A-381.

—NH—CH₂—

—(CH₂)₄— A-382.

—NH—CH₂—

—(CH₂)₄— A-383.

—NH—CH₂—

—(CH₂)₄— A-384.

—NH—CH₂—

—(CH₂)₄— A-385.

—(CH₂)₄— A-386.

—(CH₂)₄— A-387.

—(CH₂)₄— A-388.

—(CH₂)₄— A-389.

—(CH₂)₄— A-390.

—(CH₂)₄— A-391.

—(CH₂)₄— A-392.

—(CH₂)₄— A-393.

—(CH₂)₂—

—(CH₂)₄— A-394.

—(CH₂)₂—

—(CH₂)₄— A-395.

—(CH₂)₂—

—(CH₂)₄— A-396.

—(CH₂)₂—

—(CH₂)₄— A-397.

—(CH₂)₂—

—(CH₂)₄₇ A-398.

—(CH₂)₂—

—(CH₂)₄— A-399.

—(CH₂)₂—

—(CH₂)₄— A-400.

—(CH₂)₂—

—(CH₂)₄— A-401.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-402.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-403.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-404.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-405.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-406.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-407.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-408.

—NH—(CH₂)₂—O— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-409.

—NH—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-410.

—NH—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-411.

—NH—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-412.

—NH—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-413.

—NH—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-414.

—NH—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-415.

—NH—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-416.

—NH—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-417.

—NH—CH₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-418.

—NH—CH₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-419.

—NH—CH₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-420.

—NH—CH₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-421.

—NH—CH₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-422.

—NH—CH₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-423.

—NH—CH₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-424.

—NH—CH₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-425.

—CH₂— —(CH₂)₂—O—(CH₂)₂— A-426.

—CH₂— —(CH₂)₂—O—(CH₂)₂— A-427.

—CH₂— —(CH₂)₂—O—(CH₂)₂— A-428.

—CH₂— —(CH₂)₂—O—(CH₂)₂— A-429.

—CH₂— —(CH₂)₂—O—(CH₂)₂— A-430.

—CH₂— —(CH₂)₂—O—(CH₂)₂— A-431.

—CH₂— —(CH₂)₂—O—(CH₂)₂— A-432.

—CH₂— —(CH₂)₂—O—(CH₂)₂— A-433.

—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-434.

—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-435.

—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-436.

—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-437.

—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-438.

—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-439.

—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-440.

—(CH₂)₂— —CH₂— —(CH₂)₂—O—(CH₂)₂— A-441.

—NH—(CH₂)₂—O—

—(CH₂)₂—O—(CH₂)₂— A-442.

—NH—(CH₂)₂—O—

—(CH₂)₂—O—(CH₂)₂— A-443.

—NH—(CH₂)₂—O—

—(CH₂)₂—O—(CH₂)₂— A-444.

—NH—(CH₂)₂—O—

—(CH₂)₂—O—(CH₂)₂— A-445.

—NH—(CH₂)₂—O—

—(CH₂)₂—O—(CH₂)₂— A-446.

—NH—(CH₂)₂—O—

—(CH₂)₂—O—(CH₂)₂— A-447.

—NH—(CH₂)₂—O—

—(CH₂)₂—O—(CH₂)₂— A-448.

—NH—(CH₂)₂—O—

—(CH₂)₂—O—(CH₂)₂— A-449.

—NH—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-450.

—NH—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-451.

—NH—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-452.

—NH—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-453.

—NH—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-454.

—NH—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-455.

—NH—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-456.

—NH—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-457.

—NH—CH₂—

—(CH₂)₂—O—(CH₂)₂— A-458.

—NH—CH₂—

—(CH₂)₂—O—(CH₂)₂— A-459.

—NH—CH₂—

—(CH₂)₂—O—(CH₂)₂— A-460.

—NH—CH₂—

—(CH₂)₂—O—(CH₂)₂— A-461.

—NH—CH₂—

—(CH₂)₂—O—(CH₂)₂— A-462.

—NH—CH₂—

—(CH₂)₂—O—(CH₂)₂— A-463.

—NH—CH₂—

—(CH₂)₂—O—(CH₂)₂— A-464.

—NH—CH₂—

—(CH₂)₂—O—(CH₂)₂— A-465.

—(CH₂)₂—O—(CH₂)₂— A-466.

—(CH₂)₂—O—(CH₂)₂— A-467.

—(CH₂)₂—O—(CH₂)₂— A-468.

—(CH₂)₂—O—(CH₂)₂— A-469.

—(CH₂)₂—O—(CH₂)₂— A-470.

—(CH₂)₂—O—(CH₂)₂— A-471.

—(CH₂)₂—O—(CH₂)₂— A-472.

—(CH₂)₂—O—(CH₂)₂— A-473.

—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-474.

—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-475.

—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-476.

—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-477.

—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-478.

—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-479.

—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂— A-480.

—(CH₂)₂—

—(CH₂)₂—O—(CH₂)₂—

Further particular compounds of the present invention are the individualderivatives (in particular tetraline and indane derivatives) of theformula (Id) as listed in the following tables 25 to 48 andphysiologically tolerated salts thereof:

Table 25

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is hydrogen, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is hydrogen and the combination of R¹,—Y-A²-X¹-, >CR^(12a)R^(12b), R^(4b) for a compound in each casecorresponds to one line of Table A (A-481 to A-640).

Table 26

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is hydrogen, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 3-F and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 27

Compounds of the formula (Id) wherein —Y¹NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4-, R² is hydrogen, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 3-Cl and the combination of R¹, —Y-A²-X¹—,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-1 to A-512).

Table 28

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is hydrogen, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 3-CF₃ and the combination of R¹, —Y-A²—X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 29

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is hydrogen, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 2-F and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 30

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is hydrogen, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 2-Cl and the combination of R¹, —Y-A²—X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 31

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 5-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is hydrogen and the combination of R¹,—Y-A²-X¹-, >CR^(12a)R^(12b), R^(4b) for a compound in each casecorresponds to one line of Table A (A-481 to A-640).

Table 32

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 5-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 3-F and the combination of R¹, —Y-A²-X¹—,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 33

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 5-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 3-Cl and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 34

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 5-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 3-CF₃ and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 35

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 5-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 2-F and the combination of R¹, —Y-A²-X¹—,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 36

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 5-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 2-Cl and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 37

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 6-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is hydrogen and the combination of R¹,—Y-A²-X¹-, >CR^(12a)R^(12b), R^(4b) for a compound in each casecorresponds to one line of Table A (A-481 to A-640).

Table 38

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 6-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 3-F and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 39

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 6-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 3-Cl and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 40

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 6-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 3-CF₃ and the combination of R¹, —Y-A²-X¹—,>CR^(12a)R^(12b), R^(4a), R^(4b) for a compound in each case correspondsto one line of Table A (A-481 to A-640).

Table 41

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 6-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 2-F and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 42

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 6-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 2-Cl and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 43

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 8-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is hydrogen and the combination of R¹,—Y-A²-X¹-, >CR^(12a)R^(12b), R^(4b) for a compound in each casecorresponds to one line of Table A (A-481 to A-640).

Table 44

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 8-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 3-F and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4a), R^(4b) for a compound in each case correspondsto one line of Table A (A-481 to A-640).

Table 45

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 8-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 3-Cl and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 46

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 8-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 3-CF₃ and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 47

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 8-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 2-F and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Table 48

Compounds of the formula (Id) wherein —Y¹—NR^(4a)R^(4b) is as definedherein and in particular represents one of the partial structures P1,P2, P3 or P4, R² is 8-F, R³ is as defined herein and in particularrepresents hydrogen, R¹⁷ is 2-Cl and the combination of R¹, —Y-A²-X¹-,>CR^(12a)R^(12b), R^(4b) for a compound in each case corresponds to oneline of Table A (A-481 to A-640).

Partial structures P1, P2, P3, and P4:

P1

P2

P3

P4

R¹ —Y—A²—X¹— >CR^(12a)R^(12b) R^(4b) A-481.

—NH—(CH₂)₂—O— —CH₂— —H A-482.

—NH—(CH₂)₂—O— —CH₂— —H A-483.

—NH—(CH₂)₂—O— —CH₂— —H A-484.

—NH—(CH₂)₂—O— —CH₂— —H A-485.

—NH—(CH₂)₂—O— —CH₂— —H A-486.

—NH—(CH₂)₂—O— —CH₂— —H A-487.

—NH—(CH₂)₂—O— —CH₂— —H A-488.

—NH—(CH₂)₂—O— —CH₂— —H A-489.

—NH—(CH₂)₂— —CH₂— —H A-490.

—NH—(CH₂)₂— —CH₂— —H A-491.

—NH—(CH₂)₂— —CH₂— —H A-492.

—NH—(CH₂)₂— —CH₂— —H A-493.

—NH—(CH₂)₂— —CH₂— —H A-494.

—NH—(CH₂)₂— —CH₂— —H A-495.

—NH—(CH₂)₂— —CH₂— —H A-496.

—NH—(CH₂)₂— —CH₂— —H A-497.

—NH—CH₂— —CH₂— —H A-498.

—NH—CH₂— —CH₂— —H A-499.

—NH—CH₂— —CH₂— —H A-500.

—NH—CH₂— —CH₂— —H A-501.

—NH—CH₂— —CH₂— —H A-502.

—NH—CH₂— —CH₂— —H A-503.

—NH—CH₂— —CH₂— —H A-504.

—NH—CH₂— —CH₂— —H A-505.

—CH₂— —H A-506.

—CH₂— —H A-507.

—CH₂— —H A-508.

—CH₂— —H A-509.

—CH₂— —H A-510.

—CH₂— —H A-511.

—CH₂— —H A-512.

—CH₂— —H A-513.

—(CH₂)₂— —CH₂— —H A-514.

—(CH₂)₂— —CH₂— —H A-515.

—(CH₂)₂— —CH₂— —H A-516.

—(CH₂)₂— —CH₂— —H A-517.

—(CH₂)₂— —CH₂— —H A-518.

—(CH₂)₂— —CH₂— —H A-519.

—(CH₂)₂— —CH₂— —H A-520.

—(CH₂)₂— —CH₂— —H A-521.

—NH—(CH₂)₂—O—

—H A-522.

—NH—(CH₂)₂—O—

—H A-523.

—NH—(CH₂)₂—O—

—H A-524.

—NH—(CH₂)₂—O—

—H A-525.

—NH—(CH₂)₂—O—

—H A-526.

—NH—(CH₂)₂—O—

—H A-527.

—NH—(CH₂)₂—O—

—H A-528.

—NH—(CH₂)₂—O—

—H A-529.

—NH—(CH₂)₂—

—H A-530.

—NH—(CH₂)₂—

—H A-531.

—NH—(CH₂)₂—

—H A-532.

—NH—(CH₂)₂—

—H A-533.

—NH—(CH₂)₂—

—H A-534.

—NH—(CH₂)₂—

—H A-535.

—NH—(CH₂)₂—

—H A-536.

—NH—(CH₂)₂—

—H A-537.

—NH—CH₂—

—H A-538.

—NH—CH₂—

—H A-539.

—NH—CH₂—

—H A-540.

—NH—CH₂—

—H A-541.

—NH—CH₂—

—H A-542.

—NH—CH₂—

—H A-543.

—NH—CH₂—

—H A-544.

—NH—CH₂—

—H A-545.

—H A-546.

—H A-547.

—H A-548.

—H A-549.

—H A-550.

—H A-551.

—H A-552.

—H A-553.

—(CH₂)₂—

—H A-554.

—(CH₂)₂—

—H A-555.

—(CH₂)₂—

—H A-556.

—(CH₂)₂—

—H A-557.

—(CH₂)₂—

—H A-558.

—(CH₂)₂—

—H A-559.

—(CH₂)₂—

—H A-560.

—(CH₂)₂—

—H A-561.

—NH—(CH₂)₂—O— —CH₂— —CH₃ A-562.

—NH—(CH₂)₂—O— —CH₂— —CH₃ A-563.

—NH—(CH₂)₂—O— —CH₂— —CH₃ A-564.

—NH—(CH₂)₂—O— —CH₂— —CH₃ A-565.

—NH—(CH₂)₂—O— —CH₂— —CH₃ A-566.

—NH—(CH₂)₂—O— —CH₂— —CH₃ A-567.

—NH—(CH₂)₂—O— —CH₂— —CH₃ A-568.

—NH—(CH₂)₂—O— —CH₂— —CH₃ A-569.

—NH—(CH₂)₂— —CH₂— —CH₃ A-570.

—NH—(CH₂)₂— —CH₂— —CH₃ A-571.

—NH—(CH₂)₂— —CH₂— —CH₃ A-572.

—NH—(CH₂)₂— —CH₂— —CH₃ A-573.

—NH—(CH₂)₂— —CH₂— —CH₃ A-574.

—NH—(CH₂)₂— —CH₂— —CH₃ A-575.

—NH—(CH₂)₂— —CH₂— —CH₃ A-576.

—NH—(CH₂)₂— —CH₂— —CH₃ A-577.

—NH—CH₂— —CH₂— —CH₃ A-578.

—NH—CH₂— —CH₂— —CH₃ A-579.

—NH —CH₂— —CH₂— —CH₃ A-580.

—NH—CH₂— —CH₂— —CH₃ A-581.

—NH—CH₂— —CH₂— —CH₃ A-582.

—NH—CH₂— —CH₂— —CH₃ A-583.

—NH—CH₂— —CH₂— —CH₃ A-584.

—NH—CH₂— —CH₂— —CH₃ A-585.

—CH₂— —CH₃ A-586.

—CH₂— —CH₃ A-587.

—CH₂— —CH₃ A-588.

—CH₂— —CH₃ A-589.

—CH₂— —CH₃ A-590.

—CH₂— —CH₃ A-591.

—CH₂— —CH₃ A-592.

—CH₂— —CH₃ A-593.

—(CH₂)₂— —CH₂— —CH₃ A-594.

—(CH₂)₂— —CH₂— —CH₃ A-595.

—(CH₂)₂— —CH₂— —CH₃ A-596.

—(CH₂)₂— —CH₂— —CH₃ A-597.

—(CH₂)₂— —CH₂— —CH₃ A-598.

—(CH₂)₂— —CH₂— —CH₃ A-599.

—(CH₂)₂— —CH₂— —CH₃ A-600.

—(CH₂)₂— —CH₂— —CH₃ A-601.

—NH—(CH₂)₂—O—

—CH₃ A-602.

—NH—(CH₂)₂—O—

—CH₃ A-603.

—NH—(CH₂)₂—O—

—CH₃ A-604.

—NH—(CH₂)₂—O—

—CH₃ A-605.

—NH—(CH₂)₂—O—

—CH₃ A-606.

—NH—(CH₂)₂—O—

—CH₃ A-607.

—NH—(CH₂)₂—O—

—CH₃ A-608.

—NH—(CH₂)₂—O—

—CH₃ A-609.

—NH—(CH₂)₂—

—CH₃ A-610.

—NH—(CH₂)₂—

—CH₃ A-611.

—NH—(CH₂)₂—

—CH₃ A-612.

—NH—(CH₂)₂—

—CH₃ A-613.

—NH—(CH₂)₂—

—CH₃ A-614.

—NH—(CH₂)₂—

—CH₃ A-615.

—NH—(CH₂)₂—

—CH₃ A-616.

—NH—(CH₂)₂—

—CH₃ A-617.

—NH—CH₂—

—CH₃ A-618.

—NH—CH₂—

—CH₃ A-619.

—NH—CH₂—

—CH₃ A-620.

—NH—CH₂—

—CH₃ A-621.

—NH—CH₂—

—CH₃ A-622.

—NH—CH₂—

—CH₃ A-623.

—NH—CH₂—

—CH₃ A-624.

—NH—CH₂—

—CH₃ A-625.

—CH₃ A-626.

—CH₃ A-627.

—CH₃ A-628.

—CH₃ A-629.

—CH₃ A-630.

—CH₃ A-631.

—CH₃ A-632.

—CH₃ A-633.

—(CH₂)₂—

—CH₃ A-634.

—(CH₂)₂—

—CH₃ A-635.

—(CH₂)₂—

—CH₃ A-636.

—(CH₂)₂—

—CH₃ A-637.

—(CH₂)₂—

—CH₃ A-638.

—(CH₂)₂—

—CH₃ A-639.

—(CH₂)₂—

—CH₃ A-640.

—(CH₂)₂—

—CH₃

Still further particular compounds of the present invention are thecompounds disclosed in preparation examples and physiologicallytolerated salts thereof. These include for each preparation example theexemplified compound as well as the corresponding free base and anyother physiologically tolerated salts of the free base (if theexemplified compound is a salt), or any physiologically tolerated saltof the free base (if the exemplified compound is a free base). Thesefurther include enantiomers, diastereomers, tautomers and any otherisomeric forms of said compounds, be they explicitly or implicitlydisclosed.

The compounds of the formula (I) can be prepared by analogy to methodswhich are well known in the art. Suitable methods for the preparation ofcompounds of formula (I) are outlined in the following schemes.

As shown in scheme 1, the compound of general formula I readilyundergoes enamine alkylation to give the compound of general formula 3.

In scheme 1, the variables X¹, R², X², X³, R⁵ are as defined herein andL is a suitable protecting group (e.g. L=Me). The process depicted inscheme 1 is also useful for obtaining tetralines, wherein X¹ isoptionally substituted alkylene or oxygen. In this case, L is a groupthat represents, or can be converted into, the desired side chainR¹—W-A¹-Q-Y-A²-.

Alternatively, compounds of formula 3 can be prepared as described inscheme 2.

As shown in scheme 2a, the compound of general formula 4 readilyundergoes alkylation, to give the compound of general formula 5.Conversion to the acid chloride and subsequent ring closure withethylene in the presence of a Lewis acid (e.g. AlCl₃) affords compound 3(e.g. J. Het. Chem., 23 (2), 343, 1986 and Bioorg. Med. Chem. Let, 17(22), 6160, 2007).

In scheme 2a, the variables X¹, R², X², X³, R⁵ are as defined herein andL, 12 are a suitable protecting group (e.g. L, L¹=Me). Compounds 3 canbe further converted to compounds of the general formula (I).

Scheme 2b depicts the general synthesis of indanones 3 using transitionmetal-catalyzed C,C-bond formation to synthesize the indanone from adiazoprecursor (cf. Tetrahedron Letters (2009), 50, 3568). L^(x) is anester moiety. The side chain containing X², X³ and R⁵ could beintroduced by an alkylation of the 1,3-dicarbonyl intermediate.Saponification of the ester moiety and decarboxylation could yieldindanone 3.

In scheme 2b, the variables X¹, R², X², X³, R³, R⁵ are as defined hereinand L is a suitable protecting group (e.g. L=Me). Compounds 3 can befurther converted to compounds of the general formula (I).

In scheme 2c, an alternative route to compounds 14 where n=0 isdepicted. A substituted 1-indanone can be functionalized in the2-position after deprotonation next to the carbonyl followed byalkylation with an electrophile bearing a protected nitrogen(PG=protective group; this includes N(PG)₂ being nitro and the adjacentcarbon in Y¹ and N(PG)₂ being nitrile). Addition of a functionalizednucleophile (e.g. Li-organyl or Grignard reagent) to the carbonyl of the1-indanone followed by elimination and hydrogenation can yield compound8. Standard protective group chemistry followed by alkylation,deprotection of the amine attached to A² and reaction with a substitutedsulfonyl chloride can yield intermediate 12.

When N(PG)₂ is a nitro group or when N(PG)₂ and the carbon in Y¹adjacent to N(PG)₂ form a nitrile group the activated C—H bond next tothe nitro or nitrile can be used for alkylation reactions with suitablyfunctionalized electrophiles to yield compounds 14 in which R^(4a) is anoptionally substituted alkylene that is bound to a carbon atom in Y¹.Alternatively the nitrogen attached to Y¹ in compound 12 can bedeprotected and substituted to yield compound 14.

In scheme 2c, the variables R¹, W, A¹, R⁹, A², X¹, X², X³, R³, R⁵, Y¹,R^(4a), R^(4b) are as defined herein and L is a suitable protectinggroup (e.g.: L=Me).

The process depicted in scheme 3 is useful for obtaining tetralines andindanes, wherein X¹ is —O— or —S—, A² is optionally substitutedalkylene, Y is —NR⁹—, and Q is —S(O)₂. Y¹ is optionally substitutedmethylene or ethylene.

In scheme 3, the variables L, R¹, W, A¹, R², R³, R^(4a), R^(4b), R⁵, R⁹,X², X³ and n are as defined herein and L² is a suitable protecting group(e.g. L²═COOEt).

Compounds 7 in which Y¹ is ethylene can be obtained from compounds 3 inanalogy to the protocol described in Helv. Chim. Acta (1989), 72,1463-70 or J. Med. Chem. (2000), 43, 4051-62 followed by reduction ofthe corresponding nitrile (e.g. with lithium aluminum hydride or boranetetrahydrofuran complex in tetrahydrofuran).

Compounds 7 in which Y¹ is methylene can be obtained from compounds 3 byHenry reaction in analogy to the protocol described in DE3901814followed by reduction of the corresponding nitro group (e.g. catalytichydrogenation with palladium on charcoal). Alternatively compounds 7 inwhich Y¹ is methylene can be obtained from compounds 3 in analogy to theprotocol described in J. Med. Chem. (2000), 43, 4051-62 followed byCurtius rearrangement of the corresponding carboxylic acid to the amine7.

Side chains containing R¹, W, A¹, A², X¹ and R⁹ and R⁵, X² and X³ aswell as the substituents R², R³, R^(4a) and R^(4b) can be introducedanalog to the protocols described in WO2009121872.

The process depicted in scheme 3a is useful for obtaining tetralines,wherein X¹ is —O— or —S—, and Y is a bond.

In scheme 3a, the variables L, L², R¹, W, A¹, Q, A², R², R³, R^(4a),R^(4b), R⁵, X², X³, Y¹, r n are as defined herein. One example forcompound R¹—W-A¹-Q-A²-Br could be CH₃—SO₂—CH₂—CH₂—Br.

Further protocols for the synthesis of compounds in which Y is a bondand W is NR⁸ are described in WO 2009/121872.

In scheme 3b, an alternative route to compound 9 is depicted. Startingfrom a functionalized beta-keto ester the hydroxymethyl intermediate canbe obtained in analogy to the protocols described in Bioorg. Med. Chem.Lett. 2005, 15, 1375. Compound 8 wherein Y¹ is a linker containing onecarbon atom can be obtained in analogy to the protocols described inBioorg. Med. Chem. Lett. 2005, 15, 1375. To obtain longer linkers Y¹with two or three carbon atoms the hydroxyl group in the hydroxymethylintermediate can either be converted to a leaving group which then canbe substituted by a cyanide or the hydroxymethyl intermediate can beoxidized to an aldehyde which can be converted in a Henry reaction tothe corresponding nitro compound. Reduction (e.g. hydrogenation) of theabove nitriles or nitro compounds followed by protection of thecorresponding amine can give the compounds 9.

In scheme 3c, an alternative route to the hydroxymethyl intermediatedescribed above is depicted. Analog to the protocols described inJournal of Organic Chemistry (1981), 46(26), 5371, U.S. Pat. No.4,927,838 orhttp://www3.interscience.wiley.com/cgi-bin/mrwhome/107610747/HOME thealdehyde can be obtained which upon reduction (e.g. hydrogenation) canyield the hydroxymethyl intermediate.

The process depicted in scheme 4 is useful for obtaining tetralines andindanes, wherein X¹ is methylene, A² is a bond, Y is —NR⁹—, and Q is—S(O)₂.

Alternatively to triflate 19, the corresponding bromide or iodide can beused to prepare compound 20.

In scheme 4, the variables R¹, W, A¹, R², R³, R^(4a), R^(4b), R⁵, R⁹,X², X³ and n are as defined herein, and L³ is a suitable protectinggroup (e.g. L³═COO^(t)Bu). Y¹ is optionally substituted methylene orethylene.

Compounds 16 with Y¹ methylene or ethylene can be obtained from compound15 in a similar fashion as compounds 7 from compounds 3.

Side chains containing R¹, W, A¹, X¹ and R⁹ and R⁵, X² and X³ as well asthe substituents R², R³, R^(4a) and R^(4b) can be introduced in analogyto the protocols described in WO2009/121872.

The process depicted in scheme 5 is useful for obtaining tetralines andindanes, wherein X¹ is optionally substituted alkylene, A² is optionallysubstituted alkylene or a bond, Y is —NR³—, and Q is —S(O)₂.

Instead of the trifluoroborate 66, the corresponding9-borabicyclo[3.3.1]non-9-yl derivative can be used to prepare compound26.

In scheme 5, the variables R¹, W, A¹, R², R³, R^(4a), R^(4b), R⁵, R⁹,X², X³, A² and n are as defined herein, and L³ is a suitable protectinggroup (e.g. L³═COO^(t)Bu). Y¹ is optionally substituted methylene orethylene.

The process depicted in scheme 6 is useful for obtaining tetralines andindanes, wherein X is —NR¹¹-, A² is optionally substituted alkylene, Yis —NR⁹—, and Q is —S(O)₂. Y¹ is optionally substituted methylene orethylene.

In scheme 6, the variables R¹, W, A¹, R², R³, R^(4a), R^(4b), R⁵, R⁹,X², X³, A² and n are as defined herein, and L⁴ is a suitable protectinggroup. Y¹ is optionally substituted methylene or ethylene.

Compounds 33, wherein R^(4a) is alkylene that is bound to a carbon atomin Y¹ can be synthesized by the processes depicted in Scheme 7 andScheme 8.

Compounds 8a and 17a can be obtained from compounds 3 and 15,respectively, in analogy to the following protocols: Wittig reagent 7aand 16a: c.f. J. Org. Chem. 2009, 74, 9191-9194, Organic Reactions 1990,38 (http://www3.interscience.wiley.com/cgi-bin/mrwhome/107610747/HOME;CAN 149:555087); Olefination followed by hydrogenation introducing theheterocyclyl moiety yielding 8a and 17a: WO2007/143823 andWO2006/102760.

Compounds 8b and 17a can be obtained from compounds 3 and 15,respectively, in analogy to the following protocols: J. Org. Chem.(2006), 71, 7885-7887 and Organic Process Research & Development 2004,8, 389-395.

Compounds 8c and 17c can be obtained from compounds 3 and 15,respectively, in analogy to the following protocols: Pyrrolidinonesynthesis: c.f. J. Med. Chem. 2005, 48, 2294-2307; reduction topyrrolidine with lithium aluminium hydride: c.f. Tetrahedron Letters(2010), 51(11), 1459-1461.

The process depicted in the following schemes is useful for obtainingcompounds of the general formula (I) in which A is a heterocycle.

As shown in scheme 13, the compound of general formula 34 readilyundergoes condensation with dimethylformamide dimethyl acetal to givethe compound of general formula 35.

As shown in the above scheme 8, the intermediate of general formula 35reacts with various nucleophiles of general formula H₂N—NH—R in analcoholic solvent preferably methanol or ethanol at a temperature ofabout 20° to 80° C. to obtain the compounds of general formulae 36 and37. In case of monosubstituted hydrazines regioisomeric products areformed. Compounds 36 and 37 can be transformed to compounds of thegeneral formula (I) as depicted in Scheme 15.

In schemes 14 the variable R is as defined herein.

Alkylation of 38 can proceed via an enamine as described in scheme 1, orvia an enolate. Compound 39 can be used in analogy to compound 3 toprepare heterocyclic analogs of formula (I) depicted in Schemes 3 to 12.In scheme 15, the variables R, R⁵, X², X³ are as defined herein.

As shown in scheme 16, the reaction of compound of general formula 34with hydroxyl(tosyloxy)iodobenzene gives the compound of formula 42.Reaction of compound of general formula 42 with 1,3-nucleophiles underappropriate conditions yield the compound of general formula 43.Compound 45 can be used in analogy to compound 3 to prepare heterocyclicanalogs of formula (I) depicted in Schemes 3 to 12. In scheme 16, thevariables R, R⁵, X², X³ are as defined herein.

As shown in scheme 17, the condensation of compound of general formula35 with reagent of general formula 49 and ammonia acetate in refluxingacetic acid give compound of general formula 47, which can be furthertransformed to compounds of general formula 48.

Compound 48 can be used in analogy to compound 3 to prepare heterocyclicanalogs of formula (I) depicted in Schemes 3 to 12. In scheme 17, thevariables R, R⁵, X², X³ are as defined herein.

As shown in scheme 18, the cyclocondensation of intermediate of generalformula 35 with the 1,3-nucleophiles of general formula 50 in thepresence of suitable organic or inorganic bases such as KOH, NaOH,NaHCO₃, sodium ethoxide, sodium methoxide, triethyl amine anddiisopropyl ethyl amine in an alcoholic solvent, preferably ethanol ormethanol, at a temperature of about 20° to 80° C. yield the compound ofgeneral formula 51, which can be transformed further to give compoundsof general formula 52. Compound 52 can be used in analogy to compound 3to prepare heterocyclic analogs of formula (I) depicted in Schemes 3 to12. In scheme 18, the variables R, R⁵, X², X³ are as defined herein.

As shown in scheme 19, the intermediate of general formula 53 readilycan undergo condensation with dimethylformamide dimethyl acetal to givethe compound of general formula 54, which reacts with variousnucleophiles of general formula H₂N—NH—R in an alcoholic solvent,preferably methanol or ethanol, at a temperature of about 20° to 80° C.to afford the compound of general formula 55 and 56. Compounds 57 and 58can be used in analogy to compound 3 to prepare heterocyclic analogs offormula (I) depicted in Schemes 3 to 12. In scheme 19, the variables R,R⁵, X², X³ are as defined herein.

As shown in scheme 20, the reaction of compound of general formula 53with hydroxyl(tosyloxy)iodobenzene gives the compound of formula 59,which reacts with 1,3-nucleophiles under appropriate conditions to yieldthe compound of general formula 60. Further transformation results incompounds of general formula 61. Compound 61 can be used analogous tocompound 3 to prepare heterocyclic analogs of formula (I) depicted inSchemes 3 to 12. In scheme 20, the variables R, R⁵, X², X³ are asdefined herein.

As shown in scheme 21, the cyclocondensation of intermediate of generalformula 54 with the 1,3-nucleophiles of general formula 50 in thepresence of suitable organic or inorganic bases such as KOH, NaOH,NaHCO₃, sodium ethoxide, sodium methoxide, triethyl amine anddiisopropyl ethyl amine in an alcoholic solvent, preferably ethanol ormethanol, at a temperature of about 20° to 80° C. yields the compound ofgeneral formula 63, which can be transformed further to give compoundsof general formula 64. Compound 64 can be used in analogy to compound 3to prepare heterocyclic analogs of formula (I) depicted in Schemes 3 to12. In scheme 21, the variables R, R⁵, X², X³ are as defined herein.

The acid addition salts of the compounds of formula (I) are prepared ina customary manner by mixing the free base with a corresponding acid,optionally in solution in an organic solvent, for example a loweralcohol, such as methanol, ethanol or propanol, an ether, such as methyltert-butyl ether or diisopropyl ether, a ketone, such as acetone ormethyl ethyl ketone, or an ester, such as ethyl acetate.

The compounds of formula (II)

wherein L is an amino-protecting group, Y is NR⁹, and A², X¹, A, R², R³,Y¹, R^(4a), R^(4b), X², X³, R⁵, n are defined as above are useful asintermediates in the preparation of GlyT1 inhibitors, in particularthose of formula (I).

Suitable amino-protecting groups are well known in the art such as thosedescribed in Protective Groups in Organic Chemistry, ed. J. F. W.McOmie, Plenum Press, 1973; and T. W. Greene & P. G. M. Wuts, ProtectiveGroups in Organic Synthesis, John Wiley & Sons, 1991.

According to a particular embodiment, L is optionally substitutedalkylcarbonyl (e.g., tert-butylcarbonyl), optionally substitutedarylcarbonyl, optionally substituted arylalkycarbonyl (e.g.,benzylcarbonyl), optionally substituted alkoxycarbonyl (e.g.,methoxycarbonyl or tert-butyloxycarbonyl), optionally substitutedaryloxycarbonyl (e.g. phenoxycarbonyl) or optionally substitutedarylalkoxycarbonyl.

The compounds of the formula (I) are capable of inhibiting the activityof glycine transporter, in particular glycine transporter 1 (GlyT1).

The utility of the compounds in accordance with the present invention asinhibiting the glycine transporter activity, in particular GlyT1activity, may be demonstrated by methodology known in the art. Forinstance, human GlyT1c expressing recombinant hGlyT1c_(—)5_CHO cells canbe used for measuring glycine uptake and its inhibition (IC₅₀) by acompound of formula (I).

Amongst the compounds of the formula (I) those are preferred whichachieve effective inhibition at low concentrations. In particular,compounds of the formula (I) are preferred which inhibit glycinetransporter 1 (GlyT1) at a level of IC₅₀<1 μMol, more preferably at alevel of IC₅₀<0.5 μMol, particularly preferably at a level of IC₅₀<0.2μMol and most preferably at a level of IC₅₀<0.1 μMol.

The compounds of the formula (I) according to the present invention arethus useful as pharmaceuticals.

The present invention therefore also relates to pharmaceuticalcompositions which comprise an inert carrier and a compound of theformula (I).

The present invention also relates to the use of the compounds of theformula (I) in the manufacture of a medicament for inhibiting theglycine transporter GlyT1, and to corresponding methods of inhibitingthe glycine transporter GlyT1.

The NMDA receptor is central to a wide range of CNS processes, and itsrole in a variety of diseases in humans or other species has beendescribed. GlyT1 inhibitors slow the removal of glycine from thesynapse, causing the level of synaptic glycine to rise. This in turnincreases the occupancy of the glycine binding site on the NMDAreceptor, which increases activation of the NMDA receptor followingglutamate release from the presynaptic terminal. Glycine transportinhibitors and in particular inhibitors of the glycine transporter GlyT1are thus known to be useful in treating a variety of neurologic andpsychiatric disorders. Further, glycine A receptors play a role in avariety of diseases in humans or other species. Increasing extracellularglycine concentrations by inhibiting glycine trans-port may enhance theactivity of glycine A receptors. Glycine transport inhibitors and inparticular inhibitors of the glycine transporter GlyT1 are thus usefulin treating a variety of neurologic and psychiatric disorders.

The present invention thus further relates to the use of the compoundsof the formula (I) for the manufacture of a medicament for treating aneurologic or psychiatric disorder, and to corresponding methods oftreating said disorders.

According to a particular embodiment, the disorder is associated withglycinergic or glutamatergic neurotransmission dysfunction.

According to a further particular embodiment, the disorder is one ormore of the following conditions or diseases: schizophrenia or apsychotic disorder including schizophrenia (paranoid, disorganized,catatonic or undifferentiated), schizophreniform disorder,schizoaffective disorder, delusional disorder, brief psychotic disorder,shared psychotic disorder, psychotic disorder due to a general medicalcondition and substance-induced psychotic disorder, including both thepositive and the negative symptoms of schizophrenia and other psychoses;cognitive disorders including dementia (associated with Alzheimer'sdisease, ischemia, multi-infarct dementia, trauma, vascular problems orstroke, HIV disease, Parkinson's disease, Huntington's disease, Pick'sdisease, Creutzfeldt-Jacob disease, perinatal hypoxia, other generalmedical conditions or substance abuse); delirium, amnestic disorders orcognitive impairment including age related cognitive decline; anxietydisorders including acute stress disorder, agoraphobia, generalizedanxiety disorder, obsessive-compulsive disorder, panic attack, panicdisorder, post-traumatic stress disorder, separation anxiety disorder,social phobia, specific phobia, substance-induced anxiety disorder andanxiety due to a general medical condition; substance-related disordersand addictive behaviors (including substance-induced delirium,persisting dementia, persisting amnestic disorder, psychotic disorder oranxiety disorder; tolerance, dependence or withdrawal from substancesincluding alcohol, amphetamines, cannabis, cocaine, hallucinogens,inhalants, nicotine, opioids, phencyclidine, sedatives, hypnotics oranxiolytics); obesity, bulimia nervosa and compulsive eating disorders;bipolar disorders, mood disorders including depressive disorders;depression including unipolar depression, seasonal depression andpost-partum depression, premenstrual syndrome (PMS) and premenstrualdysphoric disorder (PDD), mood disorders due to a general medicalcondition, and substance-induced mood disorders; learning disorders,pervasive developmental disorder including autistic disorder, attentiondeficit disorders including attention-deficit hyperactivity disorder(ADHD) and conduct disorder; movement disorders, including akinesias andakinetic-rigid syndromes (including Parkinson's disease, drug-inducedparkinsonism, postencephalitic parkinsonism, progressive supranuclearpalsy, multiple system atrophy, corticobasal degeneration,parkinsonism-ALS dementia complex and basal ganglia calcification),medication-induced parkinsonism (such as neuroleptic-inducedparkinsonism, neuroleptic malignant syndrome, neuroleptic-induced acutedystonia, neuroleptic-induced acute akathisia, neuroleptic-inducedtardive dyskinesia and medication-induced postural tremor), Gilles de laTourette's syndrome, epilepsy, muscular spasms and disorders associatedwith muscular spasticity or weakness including tremors; dyskinesias[including tremor (such as rest tremor, postural tremor and intentiontremor), chorea (such as Sydenham's chorea, Huntington's disease, benignhereditary chorea, neuroacanthocytosis, symptomatic chorea, drug-inducedchorea and hemiballism), myoclonus (including generalised myoclonus andfocal myoclonus), tics (including simple tics, complex tics andsymptomatic tics), and dystonia (including generalised dystonia such asiodiopathic dystonia, drug-induced dystonia, symptomatic dystonia andparoxymal dystonia, and focal dystonia such as blepharospasm,oromandibular dystonia, spasmodic dysphonia, spasmodic torticollis,axial dystonia, dystonic writer's cramp and hemiplegic dystonia)];urinary incontinence; neuronal damage including ocular damage,retinopathy or macular degeneration of the eye, tinnitus, hearingimpairment and loss, and brain edema; emesis; and sleep disordersincluding insomnia and narcolepsy.

According to a further particular embodiment, the disorder is pain, inparticular chronic pain and especially neuropathic pain.

Pain can be classified as acute and chronic pain. Acute pain and chronicpain differ in their etiology, pathophysiology, diagnosis and treatment.

Acute pain, which occurs following tissue injury, is self-limiting,serves as an alert to ongoing tissue damage and following tissue repairit will usually subside. There are minimal psychological symptomsassociated with acute pain apart from mild anxiety. Acute pain isnociceptive in nature and occurs following chemical, mechanical andthermal stimulation of A-delta and C-polymodal pain receptors.

Chronic pain, on the other hand, serves no protective biologicalfunction. Rather than being the symptom of tissue damage it is a diseasein its own right. Chronic pain is unrelenting and not self-limiting andcan persist for years, perhaps decades after the initial injury. Chronicpain can be refractory to multiple treatment regimes. Psychologicalsymptoms associated with chronic pain include chronic anxiety, fear,depression, sleeplessness and impairment of social interaction. Chronicnon-malignant pain is predominantly neuropathic in nature and involvesdamage to either the peripheral or central nervous systems.

Acute pain and chronic pain are caused by different neuro-physiologicalprocesses and therefore tend to respond to different types oftreatments. Acute pain can be somatic or visceral in nature. Somaticpain tends to be a well localised, constant pain and is described assharp, aching, throbbing or gnawing. Visceral pain, on the other hand,tends to be vague in distribution, paroxysmal in nature and is usuallydescribed as deep, aching, squeezing or colicky in nature. Examples ofacute pain include post-operative pain, pain associated with trauma andthe pain of arthritis. Acute pain usually responds to treatment withopioids or non-steroidal anti-inflammatory drugs.

Chronic pain, in contrast to acute pain, is described as burning,electric, tingling and shooting in nature. It can be continuous orparoxysmal in presentation. The hallmarks of chronic pain are chronicallodynia and hyperalgesia. Allodynia is pain resulting from a stimulusthat normally does not elicit a painful response, such as a light touch.Hyperalgesia is an increased sensitivity to normally painful stimuli.Primary hyperalgesia occurs immediately within the area of the injury.Secondary hyperalgesia occurs in the undamaged area surrounding theinjury. Examples of chronic pain include complex regional pain syndrome,pain arising from peripheral neuropathies, post-operative pain, chronicfatigue syndrome pain, tension-type headache, pain arising frommechanical nerve injury and severe pain associated with diseases such ascancer, metabolic disease, neurotropic viral disease, neurotoxicity,inflammation, multiple sclerosis or any pain arising as a consequence ofor associated with stress or depressive illness.

Although opioids are cheap and effective, serious and potentiallylife-threatening side effects occur with their use, most notablyrespiratory depression and muscle rigidity. In addition the doses ofopioids which can be administered are limited by nausea, emesis,constipation, pruritis and urinary retention, often resulting inpatients electing to receive suboptimal pain control rather than sufferthese distressing side-effects. Furthermore, these side-effects oftenresult in patients requiring extended hospitalization. Opioids arehighly addictive and are scheduled drugs in many territories.

The compounds of formula (I) are particularly useful in the treatment ofschizophrenia, bipolar disorder, depression including unipolardepression, seasonal depression and post-partum depression, premenstrualsyndrome (PMS) and premenstrual dysphoric disorder (PDD), learningdisorders, pervasive developmental disorder including autistic disorder,attention deficit disorders including Attention-Deficit/HyperactivityDisorder, tic disorders including Tourette's disorder, anxiety disordersincluding phobia and post traumatic stress disorder, cognitive disordersassociated with dementia, AIDS dementia, Alzheimer's, Parkinson's,Huntington's disease, spasticity, myoclonus, muscle spasm, tinnitus andhearing impairment and loss are of particular importance.

Particular cognitive disorders are dementia, delirium, amnesticdisorders and cognitive impairment including age-related cognitivedecline.

Particular anxiety disorders are generalized anxiety disorder,obsessive-compulsive disorder and panic attack.

Particular schizophrenia or psychosis pathologies are paranoid,disorganized, catatonic or undifferentiated schizophrenia andsubstance-induced psychotic disorder.

Particular neurologic disorders that can be treated with the compoundsof the formula (I) include in particular a cognitive disorder such asdementia, cognitive impairment, attention deficit hyperactivitydisorder.

Particular psychiatric disorders that can be treated with the compoundsof the formula (I) include in particular an anxiety disorder, a mooddisorder such as depression or a bipolar disorder, schizophrenia, apsychotic disorder.

Within the context of the treatment, the use according to the inventionof the compounds of the formula (I) involves a method. In this method,an effective quantity of one or more compounds or the formula (I), as arule formulated in accordance with pharmaceutical and veterinarypractice, is administered to the individual to be treated, preferably amammal, in particular a human being. Whether such a treatment isindicated, and in which form it is to take place, depends on theindividual case and is subject to medical assessment (diagnosis) whichtakes into consideration signs, symptoms and/or malfunctions which arepresent, the risks of developing particular signs, symptoms and/ormalfunctions, and other factors.

As a rule, the treatment is effected by means of single or repeateddaily administration, where appropriate together, or alternating, withother drugs or drug-containing preparations.

The invention also relates to the manufacture of pharmaceuticalcompositions for treating an individual, preferably a mammal, inparticular a human being. Thus, the compounds of the formula (I) arecustomarily administered in the form of pharmaceutical compositionswhich comprise an inert carrier (e.g. a pharmaceutically acceptableexcipient) together with at least one compound according to theinvention and, where appropriate, other drugs. These compositions can,for example, be administered orally, rectally, transdermally,subcutaneously, intravenously, intramuscularly or intranasally.

Examples of suitable pharmaceutical formulations are solid medicinalforms, such as powders, granules, tablets, in particular film tablets,lozenges, sachets, cachets, sugar-coated tablets, capsules, such as hardgelatin capsules and soft gelatin capsules, suppositories or vaginalmedicinal forms, semisolid medicinal forms, such as ointments, creams,hydrogels, pastes or plasters, and also liquid medicinal forms, such assolutions, emulsions, in particular oil-in-water emulsions, suspensions,for example lotions, injection preparations and infusion preparations,and eyedrops and eardrops. Implanted release devices can also be usedfor administering inhibitors according to the invention. In addition, itis also possible to use liposomes or microspheres.

When producing the compositions, the compounds according to theinvention are optionally mixed or diluted with one or more carriers(excipients). Carriers (excipients) can be solid, semisolid or liquidmaterials which serve as vehicles, carriers or medium for the activecompound.

Suitable carriers (excipients) are listed in the specialist medicinalmonographs. In addition, the formulations can comprise pharmaceuticallyacceptable auxiliary substances, such as wetting agents; emulsifying andsuspending agents; preservatives; antioxidants; antiirritants; chelatingagents; coating auxiliaries; emulsion stabilizers; film formers; gelformers; odor masking agents; taste corrigents; resin; hydrocolloids;solvents; solubilizers; neutralizing agents; diffusion accelerators;pigments; quaternary ammonium compounds; refatting and overfattingagents; raw materials for ointments, creams or oils; siliconederivatives; spreading auxiliaries; stabilizers; sterilants; suppositorybases; tablet auxiliaries, such as binders, fillers, glidants,disintegrants or coatings; propellants; drying agents; opacifiers;thickeners; waxes; plasticizers and white mineral oils. A formulation inthis regard is based on specialist knowledge as described, for example,in Fiedler, H. P., Lexikon der Hilfsstoffe für Pharmazie, Kosmetik andangrenzende Gebiete [Encyclopedia of auxiliary substances for pharmacy,cosmetics and related fields], 4^(th) edition, Aulendorf:ECVE-ditio-Cantor-Verlag, 1996.

The compounds of formula (I) may also be suitable for combination withother therapeutic agents.

Thus, the present invention also provides:

i) a combination comprising a compound of formula (I) with one or morefurther therapeutic agents;ii) a pharmaceutical composition comprising a combination product asdefined in i) above and at least one carrier, diluent or excipient;iii) the use of a combination as defined in i) above in the manufactureof a medicament for treating or preventing a disorder, disease orcondition as defined herein;iv) a combination as defined in i) above for use in treating orpreventing a disorder, disease or condition as defined herein;v) a kit-of-parts for use in the treatment of a disorder, disease orcondition as defined herein, comprising a first dosage form comprising acompound of formula (I) and one or more further dosage forms eachcomprising one or more further therapeutic agents for simultaneoustherapeutic administration,vi) a combination as defined in i) above for use in therapy;vii) a method of treatment or prevention of a disorder, disease orcondition as defined herein comprising administering an effective amountof a combination as defined in i) above;viii) a combination as defined in i) above for treating or preventing adisorder, disease or condition as defined herein.

The combination therapies of the invention may be administeredadjunctively. By adjunctive administration is meant the coterminous oroverlapping administration of each of the components in the form ofseparate pharmaceutical compositions or devices. This regime oftherapeutic administration of two or more therapeutic agents is referredto generally by those skilled in the art and herein as adjunctivetherapeutic administration; it is also known as add-on therapeuticadministration. Any and all treatment regimes in which a patientreceives separate but coterminous or overlapping therapeuticadministration of the compounds of formula (I) and at least one furthertherapeutic agent are within the scope of the current invention. In oneembodiment of adjunctive therapeutic administration as described herein,a patient is typically stabilised on a therapeutic administration of oneor more of the components for a period of time and then receivesadministration of another component.

The combination therapies of the invention may also be administeredsimultaneously. By simultaneous administration is meant a treatmentregime wherein the individual components are administered together,either in the form of a single pharmaceutical composition or devicecomprising or containing both components, or as separate compositions ordevices, each comprising one of the components, administeredsimultaneously. Such combinations of the separate individual componentsfor simultaneous combination may be provided in the form of akit-of-parts.

In a further aspect, the invention provides a method of treatment of apsychotic disorder by adjunctive therapeutic administration of compoundsof formula (I) to a patient receiving therapeutic administration of atleast one antipsychotic agent. In a further aspect, the inventionprovides the use of compounds of formula (I) in the manufacture of amedicament for adjunctive therapeutic administration for the treatmentof a psychotic disorder in a patient receiving therapeuticadministration of at least one antipsychotic agent. The inventionfurther provides compounds of formula (I) for use for adjunctivetherapeutic administration for the treatment of a psychotic disorder ina patient receiving therapeutic administration of at least oneantipsychotic agent.

In a further aspect, the invention provides a method of treatment of apsychotic disorder by adjunctive therapeutic administration of at leastone antipsychotic agent to a patient receiving therapeuticadministration of compounds of formula (I). In a further aspect, theinvention provides the use of at least one antipsychotic agent in themanufacture of a medicament for adjunctive therapeutic administrationfor the treatment of a psychotic disorder in a patient receivingtherapeutic administration of compounds of formula (I). The inventionfurther provides at least one antipsychotic agent for adjunctivetherapeutic administration for the treatment of a psychotic disorder ina patient receiving therapeutic administration of compounds of formula(I).

In a further aspect, the invention provides a method of treatment of apsychotic disorder by simultaneous therapeutic administration ofcompounds of formula (I) in combination with at least one antipsychoticagent. The invention further provides the use of a combination ofcompounds of formula (I) and at least one antipsychotic agent in themanufacture of a medicament for simultaneous therapeutic administrationin the treatment of a psychotic disorder. The invention further providesa combination of compounds of formula (I) and at least one antipsychoticagent for simultaneous therapeutic administration in the treatment of apsychotic disorder. The invention further provides the use of compoundsof formula (I) in the manufacture of a medicament for simultaneoustherapeutic administration with at least one antipsychotic agent in thetreatment of a psychotic disorder. The invention further providescompounds of formula (I) for use for simultaneous therapeuticadministration with at least one antipsychotic agent in the treatment ofa psychotic disorder. The invention further provides the use of at leastone antipsychotic agent in the manufacture of a medicament forsimultaneous therapeutic administration with compounds of formula (I) inthe treatment of a psychotic disorder. The invention further provides atleast one antipsychotic agent for simultaneous therapeuticadministration with compounds of formula (I) in the treatment of apsychotic disorder.

In further aspects, the invention provides a method of treatment of apsychotic disorder by simultaneous therapeutic administration of apharmaceutical composition comprising compounds of formula (I) and atleast one mood stabilising or antimanic agent, a pharmaceuticalcomposition comprising compounds of formula (I) and at least one moodstabilising or antimanic agent, the use of a pharmaceutical compositioncomprising compounds of formula (I) and at least one mood stabilising orantimanic agent in the manufacture of a medicament for the treatment ofa psychotic disorder, and a pharmaceutical composition comprisingcompounds of formula (I) and at least one mood stabilising or antimanicagent for use in the treatment of a psychotic disorder.

Antipsychotic agents include both typical and atypical antipsychoticdrugs. Examples of antipsychotic drugs that are useful in the presentinvention include, but are not limited to: butyrophenones, such ashaloperidol, pimozide, and droperidol; phenothiazines, such aschlorpromazine, thioridazine, mesoridazine, trifluoperazine,perphenazine, fluphenazine, thiflupromazine, prochlorperazine, andacetophenazine; thioxanthenes, such as thiothixene and chlorprothixene;thienobenzodiazepines; dibenzodiazepines; benzisoxazoles;dibenzothiazepines; imidazolidinones; benziso- thiazolyl-piperazines;triazine such as lamotrigine; dibenzoxazepines, such as loxapine;dihydroindolones, such as molindone; aripiprazole; and derivativesthereof that have antipsychotic activity.

Examples of tradenames and suppliers of selected antipsychotic drugs areas follows: clozapine (available under the tradename CLOZARIL®, fromMylan, Zenith Goldline, UDL, Novartis); olanzapine (available under thetradename ZYPREX®, from Lilly); ziprasidone (available under thetradename GEODON®, from Pfizer); risperidone (available under thetradename RISPERDAL®, from Janssen); quetiapine fumarate (availableunder the tradename SEROQUEL®, from AstraZeneca); haloperidol (availableunder the tradename HALDOL®, from Ortho-McNeil); chlorpromazine(available under the tradename THORAZINE®, from SmithKline Beecham(GSK)); fluphenazine (available under the tradename PROLIXIN®, fromApothecon, Copley, Schering, Teva, and American Pharmaceutical Partners,Pasadena); thiothixene (available under the tradename NAVANE®, fromPfizer); trifluoperazine(10-[3-(4-methyl-1-piperazinyl)propyl]-2-(trifluoromethyl)phenothiazinedihydrochloride, available under the tradename STELAZINE®, from SmithKlein Beckman); perphenazine (available under the tradename TRILAFON®;from Schering); thioridazine (available under the tradename MELLARIL®;from Novartis, Roxane, HiTech, Teva, and Alpharma); molindone (availableunder the tradename MOBAN®, from Endo); and loxapine (available underthe tradename LOXITANE(D; from Watson). Furthermore, benperidol(Glianimon®), perazine (Taxilan®) or melperone (Eunerpan®) may be used.Other antipsychotic drugs include promazine (available under thetradename SPARINE®), triflurpromazine (available under the tradenameVESPRI N®), chlorprothixene (available under the tradename TARACTAN®),droperidol (available under the tradename INAPSINE®), acetophenazine(available under the tradename TINDAL®), prochlorperazine (availableunder the tradename COMPAZINE®), methotrimeprazine (available under thetradename NOZINAN®), pipotiazine (available under the tradenamePIPOTRIL®), ziprasidone, and hoperidone.

In a further aspect, the invention provides a method of treatment of aneurodegenerative disorder such as Alzheimer Disease by adjunctivetherapeutic administration of compounds of formula (I) to a patientreceiving therapeutic administration of at least one agent suitable forthe treatment of a neurodegenerative disorder such as Alzheimer Disease.In a further aspect, the invention provides the use of compounds offormula (I) in the manufacture of a medicament for adjunctivetherapeutic administration for the treatment of a neurodegenerativedisorder such as Alzheimer Disease in a patient receiving therapeuticadministration of at least one agent suitable for the treatment of aneurodegenerative disorder such as Alzheimer Disease. The inventionfurther provides compounds of formula (I) for use for adjunctivetherapeutic administration for the treatment of a neurodegenerativedisorder such as Alzheimer Disease in a patient receiving therapeuticadministration of at least one agent suitable for the treatment of aneurodegenerative disorder such as Alzheimer Disease.

In a further aspect, the invention provides a method of treatment of aneurodegenerative disorder such as Alzheimer Disease by adjunctivetherapeutic administration of at least one agent suitable for thetreatment of a neurodegenerative disorder such as Alzheimer Disease to apatient receiving therapeutic administration of compounds of formula(I). In a further aspect, the invention provides the use of at least oneagent suitable for the treatment of a neurodegenerative disorder such asAlzheimer Disease in the manufacture of a medicament for adjunctivetherapeutic administration for the treatment of a neurodegenerativedisorder such as Alzheimer Disease in a patient receiving therapeuticadministration of compounds of formula (I). The invention furtherprovides at least one agent suitable for the treatment of aneurodegenerative disorder such as Alzheimer Disease for adjunctivetherapeutic administration for the treatment of a neurodegenerativedisorder such as Alzheimer Disease in a patient receiving therapeuticadministration of compounds of formula (I).

In a further aspect, the invention provides a method of treatment of aneurodegenerative disorder such as Alzheimer Disease by simultaneoustherapeutic administration of compounds of formula (I) in combinationwith at least one agent suitable for the treatment of aneurodegenerative disorder such as Alzheimer Disease. The inventionfurther provides the use of a combination of compounds of formula (I)and at least one agent suitable for the treatment of a neurodegenerativedisorder such as Alzheimer Disease in the manufacture of a medicamentfor simultaneous therapeutic administration in the treatment of aneurodegenerative disorder such as Alzheimer Disease. The inventionfurther provides a combination of compounds of formula (I) and at leastone agent suitable for the treatment of a neurodegenerative disordersuch as Alzheimer Disease for simultaneous therapeutic administration inthe treatment of a neurodegenerative disorder such as Alzheimer Disease.The invention further provides the use of compounds of formula (I) inthe manufacture of a medicament for simultaneous therapeuticadministration with at least one agent suitable for the treatment of aneurodegenerative disorder such as Alzheimer Disease in the treatment ofa neurodegenerative disorder such as Alzheimer Disease. The inventionfurther provides compounds of formula (I) for use for simultaneoustherapeutic administration with at least one agent suitable for thetreatment of a neurodegenerative disorder such as Alzheimer Disease inthe treatment of a neurodegenerative disorder such as Alzheimer Disease.The invention further provides the use of at least one agent suitablefor the treatment of a neurodegenerative disorder such as AlzheimerDisease in the manufacture of a medicament for simultaneous therapeuticadministration with compounds of formula (I) in the treatment of aneurodegenerative disorder such as Alzheimer Disease. The inventionfurther provides at least one agent suitable for the treatment of aneurodegenerative disorder such as Alzheimer Disease for simultaneoustherapeutic administration with compounds of formula (I) in thetreatment of a neurodegenerative disorder such as Alzheimer Disease.

Examples of agents suitable for the treatment of a neurodegenerativedisorder such as Alzheimer Disease that are-useful in the presentinvention include, but are not limited to: cholinesterase inhibitors,agents targeting nicotinic or muscarinic acetylcholine receptors, NMDAreceptors, amyloid formation, mitochondrial dysfunctions, diseaseassociated calpain activity, neuroinflamation, tumor necrosis factorreceptors, NF-kappaB, peroxisome proliferator activator receptor gamma,Apolipoprotein E variant 4 (ApoE4), disease-associated increase of theHPA axis, epileptic discharges, vascular dysfunction, vascular riskfactors, and oxidative stress.

Suitable cholinesterase inhibitors which may be used in combination withthe compounds of the inventions include for example tacrine, donepezil,galantamine and rivastigmine.

Suitable NMDA receptors targeting agents which may be used incombination with the compounds of the inventions include for examplememantine.

Suitable agents affecting increased HPA axis activity which may be usedin combination with the compounds of the inventions include for exampleCRF1 antagonists or V1b antagonists.

In a further aspect therefore, the invention provides a method oftreatment of pain by adjunctive therapeutic administration of compoundsof formula (I) to a patient receiving therapeutic administration of atleast one agent suitable for the treatment of pain. In a further aspect,the invention provides the use of compounds of formula (I) in themanufacture of a medicament for adjunctive therapeutic administrationfor the treatment of pain in a patient receiving therapeuticadministration of at least one agent suitable for the treatment of pain.The invention further provides compounds of formula (I) for use foradjunctive therapeutic administration for the treatment of pain in apatient receiving therapeutic administration of at least one agentsuitable for the treatment of pain.

In a further aspect, the invention provides a method of treatment ofpain by adjunctive therapeutic administration of at least one agentsuitable for the treatment of pain to a patient receiving therapeuticadministration of compounds of formula (I). In a further aspect, theinvention provides the use of at least one agent suitable for thetreatment of pain in the manufacture of a medicament for adjunctivetherapeutic administration for the treatment of pain in a patientreceiving therapeutic administration of compounds of formula (I).

The invention further provides at least one agent suitable for thetreatment of pain for adjunctive therapeutic administration for thetreatment of pain in a patient receiving therapeutic administration ofcompounds of formula (I).

In a further aspect, the invention provides a method of treatment ofpain by simultaneous therapeutic administration of compounds of formula(I) in combination with at least one agent suitable for the treatment ofpain. The invention further provides the use of a combination ofcompounds of formula (I) and at least one agent suitable for thetreatment of pain in the manufacture of a medicament for simultaneoustherapeutic administration in the treatment of pain. The inventionfurther provides a combination of compounds of formula (I) and at leastone agent suitable for the treatment of pain for simultaneoustherapeutic administration in the treatment of pain. The inventionfurther provides the use of compounds of formula (I) in the manufactureof a medicament for simultaneous therapeutic administration with atleast one agent suitable for the treatment of pain in the treatment ofpain. The invention further provides compounds of formula (I) for usefor simultaneous therapeutic administration with at least one agentsuitable for the treatment of pain in the treatment of pain. Theinvention further provides the use of at least one agent suitable forthe treatment of pain in the manufacture of a medicament forsimultaneous therapeutic administration with compounds of formula (I) inthe treatment of pain. The invention further provides at least one agentsuitable for the treatment of pain for simultaneous therapeuticadministration with compounds of formula (I) in the treatment of pain.

Examples of agents suitable for the treatment of pain that are useful inthe present invention include, but are not limited to: NSAIDs(Nonsteroidal Antiinflammatory Drugs), anti-convulsant drugs such ascarbamazepine and gabapentin, sodium channel blockers, anti-depressantdrugs, cannabinoids and local anesthetics.

Suitable agents used in combination with the compounds of the inventionsinclude for example celecoxib, etoricoxib, lumiracoxib, paracetamol,tramadol, methadone, venlafaxine, imipramine, duloxetine, bupropion,gabapentin, pregabalin, lamotrigine, fentanyl, parecoxib, nefopam,remifentanil, pethidine, diclofenac, rofecoxib, nalbuphine, sufentanil,pethidine, diamorphine and butorphanol.

It will be appreciated by those skilled in the art that the compoundsaccording to the invention may advantageously be used in conjunctionwith one or more other therapeutic agents, for instance, antidepressantagents such as 5HT3 antagonists, serotonin agonists, NK-1 antagonists,selective serotonin reuptake inhibitors (SSRI), noradrenaline re-uptakeinhibitors (SNRI), tricyclic antidepressants, dopaminergicantidepressants, H3 antagonists, 5HT1A antagonists, 5HT1 B antagonists,5HT1 D antagonists, D1 agonists, M1 agonists and/or anticonvulsantagents, as well as cognitive enhancers.

Suitable 5HT3 antagonists which may be used in combination of thecompounds of the inventions include for example ondansetron,granisetron, metoclopramide.

Suitable serotonin agonists which may be used in combination with thecompounds of the invention include sumatriptan, rauwolscine, yohimbine,metoclopramide.

Suitable SSRIs which may be used in combination with the compounds ofthe invention include fluoxetine, citalopram, femoxetine, fluvoxamine,paroxetine, indalpine, sertraline, zimeldine.

Suitable SNRIs which may be used in combination with the compounds ofthe invention include venlafaxine and reboxetine.

Suitable tricyclic antidepressants which may be used in combination witha compound of the invention include imipramine, amitriptiline,chlomipramine and nortriptiline.

Suitable dopaminergic antidepressants which may be used in combinationwith a compound of the invention include bupropion and amineptine.

Suitable anticonvulsant agents which may be used in combination of thecompounds of the invention include for example divaiproex, carbamazepineand diazepam.

The following examples serve to explain the invention without limitingit.

The compounds were characterized by mass spectrometry, generallyrecorded via HPLC-MS in a fast gradient on C18-material(electrospray-ionisation (ESI) mode).

Preparation Examples

The following compounds were obtained or can be obtained using theprocedures described herein.

1

N-[2-[3-benzyl-2- (methylaminomethyl)indan-5-yl]oxyethyl]-1-cyclopropyl- methanesulfonamide 2

N-[2-[3-benzyl-2- (methylaminomethyl)indan-5-yl]oxyethyl]cyclobutanesulfonamide 3

N-[2-[3-benzyl-2- (methylaminomethyl)indan-5-yl]oxyethyl]-1-methyl-imidazole-4- sulfonamide 4

N-[2-[3-benzyl-2- (methylaminomethyl)indan-5-yl]oxyethyl]-1-methyl-pyrazole-4- sulfonamide 5

N-[[3-benzyl-2- (methylaminomethyl)indan-5- yl]methyl]-1-cyclopropyl-methanesulfonamide 6

N-[2-[3-benzyl-2- (methylaminomethyl)indan-5- yl]ethyl]-1-cyclopropyl-methanesulfonamide 7

N-[[3-benzyl-2- (methylaminomethyl)indan-5-yl]methyl]cyclobutanesulfonamide 8

N-[2-[3-benzyl-2- (methylaminomethyl)indan-5-yl]ethyl]cyclobutanesulfonamide 9

N-[[3-benzyl-2- (methylaminomethyl)indan-5-yl]methyl]-1-methyl-imidazole-4- sulfonamide 10

N-[2-[3-benzyl-2- (methylaminomethyl)indan-5-yl]ethyl]-1-methyl-imidazole-4- sulfonamide 11

N-[[3-benzyl-2- (methylaminomethyl)indan-5-yl]methyl]-1-methyl-pyrazole-4- sulfonamide 12

N-[2-[3-benzyl-2- (methylaminomethyl)indan-5-yl]ethyl]-1-methyl-pyrazole-4- sulfonamide 13

N-[2-[3-benzyl-6-fluoro-2- (methylaminomethyl)indan-5-yl]oxyethyl]-1-cyclopropyl- methanesulfonamide 14

N-[2-[3-benzyl-6-fluoro-2- (methylaminomethyl)indan-5-yl]oxyethyl]cyclobutanesulfonamide 15

N-[2-[3-benzyl-6-fluoro-2- (methylaminomethyl)indan-5-yl]oxyethyl]-1-methyl-imidazole-4- sulfonamide 16

N-[2-[3-benzyl-6-fluoro-2- (methylaminomethyl)indan-5-yl]oxyethyl]-1-methyl-pyrazole-4- sulfonamide 17

N-[[3-benzyl-6-fluoro-2- (methylaminomethyl)indan-5-yl]methyl]-1-cyclopropyl- methanesulfonamide 18

N-[2-[3-benzyl-6-fluoro-2- (methylaminomethyl)indan-5-yl]ethyl]-1-cyclopropyl- methanesulfonamide 19

N-[[3-benzyl-6-fluoro-2- (methylaminomethyl)indan-5-yl]methyl]cyclobutanesulfonamide 20

N-[2-[3-benzyl-6-fluoro-2- (methylaminomethyl)indan-5-yl]ethyl]cyclobutanesulfonamide 21

N-[[3-benzyl-6-fluoro-2- (methylaminomethyl)indan-5-yl]methyl]-1-methyl-imidazole-4- sulfonamide 22

N-[2-[3-benzyl-6-fluoro-2- (methylaminomethyl)indan-5-yl]ethyl]-1-methyl-imidazole-4- sulfonamide 23

N-[[3-benzyl-6-fluoro-2- (methylaminomethyl)indan-5-yl]methyl]-1-methyl-pyrazole-4- sulfonamide 24

N-[2-[3-benzyl-6-fluoro-2- (methylaminomethyl)indan-5-yl]ethyl]-1-methyl-pyrazole-4- sulfonamide 25

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-indan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide 26

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-indan-5-yl]oxyethyl]cyclobutanesulfonamide 27

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-indan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide 28

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-indan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide 29

N-[[2-(azetidin-1-ylmethyl)-3-benzyl- indan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide 30

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-indan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide 31

N-[[2-(azetidin-1-ylmethyl)-3-benzyl- indan-5-yl]methyl]cyclobutanesulfonamide 32

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-indan-5-yl]ethyl]cyclobutanesulfonamide 33

N-[[2-(azetidin-1-ylmethyl)-3-benzyl- indan-5-yl]methyl]-1-methyl-imidazole-4-sulfonamide 34

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-indan-5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide 35

N-[[2-(azetidin-1-ylmethyl)-3-benzyl- indan-5-yl]methyl]-1-methyl-pyrazole-4-sulfonamide 36

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-indan-5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide 37

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-6-fluoro-indan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide 38

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-6-fluoro-indan-5-yl]oxyethyl]cyclobutanesulfonamide 39

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-6-fluoro-indan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide 40

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-6-fluoro-indan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide 41

N-[[2-(azetidin-1-ylmethyl)-3-benzyl- 6-fluoro-indan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide 42

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-6-fluoro-indan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide 43

N-[[2-(azetidin-1-ylmethyl)-3-benzyl- 6-fluoro-indan-5-yl]methyl]cyclobutanesulfonamide 44

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-6-fluoro-indan-5-yl]ethyl]cyclobutanesulfonamide 45

N-[[2-(azetidin-1-ylmethyl)-3-benzyl- 6-fluoro-indan-5-yl]methyl]-1-methyl-imidazole-4-sulfonamide 46

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-6-fluoro-indan-5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide 47

N-[[2-(azetidin-1-ylmethyl)-3-benzyl- 6-fluoro-indan-5-yl]methyl]-1-methyl-pyrazole-4-sulfonamide 48

N-[2-[2-(azetidin-1-ylmethyl)-3- benzyl-6-fluoro-indan-5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide 49

1-cyclopropyl-N-[2-[3-[(3- fluorophenyl)methyl]-2-(methylaminomethyl)indan-5- yl]oxyethyl]methanesulfonamide 50

N-[2-[3-[(3-fluorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]oxyethyl]cyclobutanesulfonamide 51

N-[2-[3-[(3-fluorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]oxyethyl]-1-methyl-imidazole-4- sulfonamide 52

N-[2-[3-[(3-fluorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]oxyethyl]-1-methyl-pyrazole-4- sulfonamide 53

1-cyclopropyl-N-[[3-[(3- fluorophenyl)methyl]-2-(methylaminomethyl)indan-5- yl]methyl]methanesulfonamide 54

1-cyclopropyl-N-[2-[3-[(3- fluorophenyl)methyl]-2-(methylaminomethyl)indan-5- yl]ethyl]methanesulfonamide 55

N-[[3-[(3-fluorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]methyl]cyclobutanesulfonamide 56

N-[2-[3-[(3-fluorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]ethyl]cyclobutanesulfonamide 57

N-[[3-[(3-fluorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]methyl]-1-methyl-imidazole-4- sulfonamide 58

N-[2-[3-[(3-fluorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]ethyl]-1-methyl-imidazole-4- sulfonamide 59

N-[[3-[(3-fluorophenyl)methyl]-2- (methylaminomethyl]indan-5-yl]methyl]-1-methyl-pyrazole-4- sulfonamide 60

N-[2-[3-[(3-fluorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]ethyl]-1-methyl-pyrazole-4- sulfonamide 61

1-cyclopropyl-N-[2-[6-fluoro-3-[(3- fluorophenyl)methyl]-2-(methylaminomethyl)indan-5- yl]oxyethyl]methanesulfonamide 62

N-[2-[6-fluoro-3-[(3- fluorophenyl)methyl]-2-(methylaminomethyl)indan-5- yl]oxyethyl]cyclobutanesulfonamide 63

N-[2-[6-fluoro-3-[(3- fluorophenyl)methyl]-2-(methylaminomethyl)indan-5- yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide 64

N-[2-[6-fluoro-3-[(3- fluorophenyl)methyl]-2-(methylaminomethyl)indan-5- yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide 65

1-cyclopropyl-N-[[6-fluoro-3-[(3- fluorophenyl)methyl]-2-(methylaminomethyl)indan-5- yl]methyl]methanesulfonamide 66

1-cyclopropyl-N-[2-[6-fluoro-3-[(3- fluorophenyl)methyl]-2-(methylaminomethyl)indan-5- yl]ethyl]methanesulfonamide 67

N-[[6-fluoro-3-[(3- fluorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]methyl]cyclobutanesulfonamide 68

N-[2-[6-fluoro-3-[(3- fluorophenyl)methyl]-2-(methylaminomethyl]indan-5- yl]ethyl]cyclobutanesulfonamide 69

N-[[6-fluoro-3-[(3- fluorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]methyl]-1-methyl-imidazole-4- sulfonamide 70

N-[2-[6-fluoro-3-[(3- fluorophenyl)methyl]-2-(methylaminomethyl)indan-5- yl]ethyl]-1-methyl-imidazole-4- sulfonamide71

N-[[6-fluoro-3-[(3- fluorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]methyl]-1-methyl-pyrazole-4- sulfonamide 72

N-[2-[6-fluoro-3-[(3- fluorophenyl)methyl]-2-(methylaminomethyl)indan-5- yl]ethyl]-1-methyl-pyrazole-4- sulfonamide73

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- fluorophenyl)methyl]indan-5-yl]oxyethyl]-1-cyclopropyl- methanesulfonamide 74

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- fluorophenyl)methyl]indan-5-yl]oxyethyl]cyclobutanesulfonamide 75

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- fluorophenyl)methyl]indan-5-yl]oxyethyl]-1-methyl-imidazole-4- sulfonamide 76

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- fluorophenyl)methyl]indan-5-yl]oxyethyl]-1-methyl-pyrazole-4- sulfonamide 77

N-[[2-(azetidin-1-ylmethyl)-3-[(3- fluorophenyl)methyl]indan-5-yl]methyl]-1-cyclopropyl- methanesulfonamide 78

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- fluorophenyl)methyl]indan-5-yl]ethyl]-1-cyclopropyl- methanesulfonamide 79

N-[[2-(azetidin-1-ylmethyl)-3-[(3- fluorophenyl)methyl]indan-5-yl]methyl]cyclobutanesulfonamide 80

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- fluorophenyl)methyl]indan-5-yl]ethyl]cyclobutanesulfonamide 81

N-[[2-(azetidin-1-ylmethyl)-3-[(3- fluorophenyl)methyl]indan-5-yl]methyl]-1-methyl-imidazole-4- sulfonamide 82

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- fluorophenyl)methyl]indan-5-yl]ethyl]-1-methyl-imidazole-4- sulfonamide 83

N-[[2-(azetidin-1-ylmethyl)-3-[(3- fluorophenyl)methyl]indan-5-yl]methyl]-1-methyl-pyrazole-4- sulfonamide 84

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- fluorophenyl)methyl]indan-5-yl]ethyl]-1-methyl-pyrazole-4- sulfonamide 85

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[(3-fluorophenyl)methyl]indan-5- yl]oxyethyl]-1-cyclopropyl-methanesulfonamide 86

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[(3-fluorophenyl)methyl]indan-5- yl]oxyethyl]cyclobutanesulfonamide 87

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[(3-fluorophenyl)methyl]indan-5- yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide 88

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[(3-fluorophenyl)methyl]indan-5- yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide 89

N-[[2-(azetidin-1-ylmethyl)-6-fluoro- 3-[(3-fluorophenyl)methyl]indan-5-yl]methyl]-1-cyclopropyl- methanesulfonamide 90

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[(3-fluorophenyl)methyl]indan-5- yl]ethyl]-1-cyclopropyl- methanesulfonamide91

N-[[2-(azetidin-1-ylmethyl)-6-fluoro- 3-[(3-fluorophenyl)methyl]indan-5-yl]methyl]cyclobutanesulfonamide 92

N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]ethyl]cyclobutanesulfonamide 93

N-[[2-(azetidin-1-ylmethyl)-6-fluoro- 3-[(3-fluorophenyl)methyl]indan-5-yl]methyl]-1-methyl-imidazole-4- sulfonamide 94

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[(3-fluorophenyl)methyl]indan-5- yl]ethyl]-1-methyl-imidazole-4- sulfonamide95

N-[[2-(azetidin-1-ylmethyl)-6-fluoro- 3-[(3-fluorophenyl)methyl]indan-5-yl]methyl]-1-methyl-pyrazole-4- sulfonamide 96

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[(3-fluorophenyl)methyl]indan-5- yl]ethyl]-1-methyl-pyrazole-4- sulfonamide97

N-[2-[3-[(3-chlorophenyl)methyl]-2- (methylaminomethyl]indan-5-yl]oxyethyl]-1-cyclopropyl- methanesulfonamide 98

N-[2-[3-[(3-chlorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]oxyethyl]cyclobutanesulfonamide 99

N-[2-[3-[(3-chlorophenyl)methyl]-2- (methylaminomethyl]indan-5-yl]oxyethyl]-1-methyl-imidazole-4- sulfonamide 100

N-[2-[3-[(3-chlorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]oxyethyl]-1-methyl-pyrazole-4- sulfonamide 101

N-[2-[3-[(3-chlorophenyl)methyl]-2- (methylaminomethyl]indan-5-yl]oxyethyl]-1-methyl-pyrazole-4- sulfonamide 102

N-[2-[3-[(3-chlorophenyl)methyl]-2- (methylaminomethyl]indan-5-yl]ethyl]-1-cyclopropyl- methanesulfonamide 103

N-[[3-[(3-chlorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]methyl]cyclobutanesulfonamide 104

N-[2-[3-[(3-chlorophenyl)methyl]-2- (methylaminomethyl]indan-5-yl]ethyl]cyclobutanesulfonamide 105

N-[[3-[(3-chlorophenyl)methyl]-2- (methylaminomethyl]indan-5-yl]methyl]-1-methyl-imidazole-4- sulfonamide 106

N-[2-[3-[(3-chlorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]ethyl]-1-methyl-imidazole-4- sulfonamide 107

N-[[3-[(3-chlorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]methyl]-1-methyl-pyrazole-4- sulfonamide 108

N-[2-[3-[(3-chlorophenyl)methyl]-2- (methylaminomethyl)indan-5-yl]ethyl]-1-methyl-pyrazole-4- sulfonamide 109

N-[2-[3-[(3-chlorophenyl)methyl]-6- fluoro-2-(methylaminomethyl)indan-5-yl]oxyethyl]-1-cyclopropyl- methanesulfonamide 110

N-[2-[3-[(3-chlorophenyl)methyl]-6- fluoro-2-(methylaminomethyl)indan-5-yl]oxyethyl]cyclobutanesulfonamide 111

N-[2-[3-[(3-chlorophenyl)methyl]-6- fluoro-2-(methylaminomethyl)indan-5-yl]oxyethyl]-1-methyl-imidazole-4- sulfonamide 112

N-[2-[3-[(3-chlorophenyl)methyl]-6- fluoro-2-(methylaminomethyl)indan-5-yl]oxyethyl]-1-methyl-pyrazole-4- sulfonamide 113

N-[[3-[(3-chlorophenyl)methyl]-6- fluoro-2-(methylaminomethyl)indan-5-yl]methyl]-1-cyclopropyl- methanesulfonamide 114

N-[2-[3-[(3-chlorophenyl)methyl]-6- fluoro-2-(methylaminomethyl)indan-5-yl]ethyl]-1-cyclopropyl- methanesulfonamide 115

N-[[3-[(3-chlorophenyl)methyl]-6- fluoro-2-(methylaminomethyl)indan-5-yl]methyl]cyclobutanesulfonamide 116

N-[2-[3-[(3-chlorophenyl)methyl]-6- fluoro-2-(methylaminomethyl)indan-5-yl]ethyl]cyclobutanesulfonamide 117

N-[[3-[(3-chlorophenyl)methyl]-6- fluoro-2-(methylaminomethyl)indan-5-yl]methyl]-1-methyl-imidazole-4- sulfonamide 118

N-[2-[3-[(3-chlorophenyl)methyl]-6- fluoro-2-(methylaminomethyl)indan-5-yl]ethyl]-1-methyl-imidazole-4- sulfonamide 119

N-[[3-[(3-chlorophenyl)methyl]-6- fluoro-2-(methylaminomethyl)indan-5-yl]methyl]-1-methyl-pyrazole-4- sulfonamide 120

N-[2-[3-[(3-chlorophenyl)methyl]-6- fluoro-2-(methylaminomethyl)indan-5-yl]ethyl]-1-methyl-pyrazole-4- sulfonamide 121

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]indan-5-yl]oxyethyl]-1-cyclopropyl- methanesulfonamide 122

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]indan-5-yl]oxyethyl]cyclobutanesulfonamide 123

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]indan-5-yl]oxyethyl]-1-methyl-imidazole-4- sulfonamide 124

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]indan-5-yl]oxyethyl]-1-methyl-pyrazole-4- sulfonamide 125

N-[[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]indan-5-yl]methyl]-1-cyclopropyl- methanesulfonamide 126

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]indan-5-yl]ethyl]-1-cyclopropyl- methanesulfonamide 127

N-[[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]indan-5-yl]methyl]cyclobutanesulfonamide 128

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]indan-5-yl]ethyl]cyclobutanesulfonamide 129

N-[[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]indan-5-yl]methyl]-1-methyl-imidazole-4- sulfonamide 130

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]indan-5-yl]ethyl]-1-methyl-imidazole-4- sulfonamide 131

N-[[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]indan-5-yl]methyl]-1-methyl-pyrazole-4- sulfonamide 132

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]indan-5-yl]ethyl]-1-methyl-pyrazole-4- sulfonamide 133

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan- 5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide 134

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]oxyethyl]cyclobutanesulfonamide 135

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]oxyethyl]-1-methyl-imidazole-4- sulfonamide 136

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan- 5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide 137

N-[[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]-6-fluoro-indan-5-yl]methyl]-1-cyclopropyl- methanesulfonamide 138

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan- 5-yl]ethyl]-1-cyclopropyl-methanesulfonamide 139

N-[[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]-6-fluoro-indan-5-yl]methyl]cyclobutanesulfonamide 140

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan- 5-yl]ethyl]cyclobutanesulfonamide141

N-[[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]-6-fluoro-indan-5-yl]methyl]-1-methyl-imidazole-4- sulfonamide 142

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan- 5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide 143

N-[[2-(azetidin-1-ylmethyl)-3-[(3- chlorophenyl)methyl]-6-fluoro-indan-5-yl]methyl]-1-methyl-pyrazole-4- sulfonamide 144

N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan- 5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide 145

1-cyclopropyl-N-[2-[2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]methanesulfonamide 146

N-[2-[2-(methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]cyclobutanesulfonamide 147

1-methyl-N-[2-[2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]imidazole-4-sulfonamide 148

1-methyl-N-[2-[2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]pyrazole-4-sulfonamide 149

1-cyclopropyl-N-[[2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]methanesulfonamide 150

1-cyclopropyl-N-[2-[2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]methanesulfonamide 151

N-[[2-(methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]cyclobutanesulfonamide 152

N-[2-[2-(methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]cyclobutanesulfonamide 153

1-methyl-N-[[2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]imidazole-4-sulfonamide 154

1-methyl-N-[2-[2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]imidazole-4-sulfonamide 155

1-methyl-N-[[2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]pyrazole-4-sulfonamide 156

1-methyl-N-[2-[2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]pyrazole-4-sulfonamide 157

1-cyclopropyl-N-[2-[6-fluoro-2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]methanesulfonamide 158

N-[2-[6-fluoro-2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]cyclobutanesulfonamide 159

N-[2-[6-fluoro-2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide 160

N-[2-[6-fluoro-2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide 161

1-cyclopropyl-N-[[6-fluoro-2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]methanesulfonamide 162

1-cyclopropyl-N-[2-[6-fluoro-2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]methanesulfonamide 163

N-[[6-fluoro-2-(methylaminomethyl)- 3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]cyclobutanesulfonamide 164

N-[2-[6-fluoro-2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]cyclobutanesulfonamide 165

N-[[6-fluoro-2-(methylaminomethyl)- 3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]-1-methyl-imidazole-4-sulfonamide 166

N-[2-[6-fluoro-2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]-1-methyl-imidazole-4-sulfonamide 167

N-[[6-fluoro-2-(methylaminomethyl)- 3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]-1-methyl-pyrazole-4-sulfonamide 168

N-[2-[6-fluoro-2- (methylaminomethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]-1-methyl-pyrazole-4- sulfonamide169

N-[2-[2-(azetidin-1-ylmethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]-1-cyclopropyl-methanesulfonamide 170

N-[2-[2-(azetidin-1-ylmethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]cyclobutanesulfonamide 171

N-[2-[2-(azetidin-1-ylmethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide 172

N-[2-[2-(azetidin-1-ylmethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide 173

N-[[2-(azetidin-1-ylmethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]-1-cyclopropyl-methanesulfonamide 174

N-[2-[2-(azetidin-1-ylmethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]-1-cyclopropyl-methanesulfonamide 175

N-[[2-(azetidin-1-ylmethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]cyclobutanesulfonamide 176

N-[2-[2-(azetidin-1-ylmethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]cyclobutanesulfonamide 177

N-[[2-(azetidin-1-ylmethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]-1-methyl-imidazole-4-sulfonamide 178

N-[2-[2-(azetidin-1-ylmethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]-1-methyl-imidazole-4-sulfonamide 179

N-[[2-(azetidin-1-ylmethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]-1-methyl-pyrazole-4-sulfonamide 180

N-[2-[2-(azetidin-1-ylmethyl)-3-[[3- (trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]-1-methyl-pyrazole-4- sulfonamide181

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]-1-cyclopropyl-methanesulfonamide 182

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]cyclobutanesulfonamide 183

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide 184

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide 185

N-[[2-(azetidin-1-ylmethyl)-6-fluoro- 3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]-1-cyclopropyl-methanesulfonamide 186

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]-1-cyclopropyl-methanesulfonamide 187

N-[[2-(azetidin-1-ylmethyl)-6-fluoro- 3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]cyclobutanesulfonamide 188

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]cyclobutanesulfonamide 189

N-[[2-(azetidin-1-ylmethyl)-6-fluoro- 3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]-1-methyl-imidazole-4-sulfonamide 190

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]-1-methyl-imidazole-4-sulfonamide 191

N-[[2-(azetidin-1-ylmethyl)-6-fluoro- 3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]methyl]-1-methyl-pyrazole-4-sulfonamide 192

N-[2-[2-(azetidin-1-ylmethyl)-6- fluoro-3-[[3-(trifluoro-methyl)phenyl]methyl]indan-5- yl]ethyl]-1-methyl-pyrazole-4- sulfonamide

Example 193 Propane-1-sulfonic acid(8-benzyl-7-cyclopropylamino-5,6,7,8-tetrahydro-naphthalen-2-ylmethyl)-amidehydrochloride

N-((7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl)propane-1-sulfonamide(51 mg, 0.137 mmol), (1-ethoxycyclopropoxy)trimethylsilane (26 mg, 0.151mmol), acetic acid (0.078 mL, 1.37 mmol), sodium cyanoborohydride (26mg, 0.411 mmol) and molecular sieve (50 mg) in methanol (1.5 mL) wereheated in the microwave at 100° C. for 25 min. The solvent wasevaporated and the crude product purified by flash chromatography(silica gel, dichloromethane, methanol) and converted into the hydrochloride. Yield: 18 mg (0.04 mmol, 29%).

ESI-MS [M+H⁺]=413 Calculated for C₂₄H₃₂N₂O₂S=412

Biological Testing

1. [³H]-Glycine uptake into recombinant CHO cells expressing humanGlyT1: Human GlyT1c expressing recombinant hGlyT1c_(—)5_CHO cells wereplated at 20,000 cells per well in 96 well Cytostar-T scintillationmicroplates (Amersham Biosciences) and cultured to sub-confluency for 24h. For glycine uptake assays the culture medium was aspirated and thecells were washed once with 100 μl HBSS (Gibco BRL, #14025-050) with 5mM L-Alanine (Merck #1007). 80 μl HBSS buffer were added, followed by10μl inhibitor or vehicle (10% DMSO) and 10 μl [³H]-glycine (TRK71,Amersham Biosciences) to a final concentration of 200 nM for initiationof glycine uptake. The plates were placed in a Wallac Microbeta(PerkinElmer) and continuously counted by solid phase scintillationspectrometry during up to 3 hours. Nonspecific uptake was determined inthe presence of 10 μM Org24598. IC₅₀ calculations were made byfour-parametric logistic nonlinear regression analysis (GraphPad Prism)using determinations within the range of linear increase of [³H]-glycineincorporation between 60 and 120 min.

2. Radioligand binding assays using recombinant CHO cell membranesexpressing human GlyT1:

Radioligand binding to human GlyT1c transporter-expressing membranes wasdetermined as described in Mezler et al., Molecular Pharmacology74:1705-1715, 2008.

We claim:
 1. Compounds of the formula (I)

wherein A is a 5- or 6-membered ring; R is R¹—W-A¹-Q-Y-A²-X¹—; R¹ ishydrogen, C₁-C₆-alkyl, C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl, halogenatedC₁-C₆-alkyl, tri(C₁-C₄-alkyl)-silyl-C₁-C₄-alkyl, hydroxy-C₁-C₄-alkyl,C₁-C₆-alkoxy-C₁-C₄-alkyl, amino-C₁-C₄-alkyl,C₁-C₆-alkylamino-C₁-C₄-alkyl, di-C₁-C₆-alkylamino-C₁-C₄-alkyl,C₁-C₆-alkylcarbonylamino-C₁-C₄-alkyl,C₁-C₆-alkyloxycarbonylamino-C₁-C₄-alkyl,C₁-C₆-alkylaminocarbonylamino-C₁-C₄-alkyl,di-C₁-C₆-alkylaminocarbonylamino-C₁-C₄-alkyl,C₁-C₆-alkylsulfonylamino-C₁-C₄-alkyl, (optionally substitutedC₆-C₁₂-aryl-C₁-C₆-alkyl)amino-C₁-C₄-alkyl, optionally substitutedC₆-C₁₂-aryl-C₁-C₄-alkyl, optionally substitutedC₃-C₁₂-heterocyclyl-C₁-C₄-alkyl, C₃-C₁₂-cycloalkyl, C₁-C₆-alkylcarbonyl,C₁-C₆-alkoxycarbonyl, halogenated C₁-C₆-alkoxycarbonyl,C₆-C₁₂-aryloxycarbonyl, aminocarbonyl, C₁-C₆-alkylaminocarbonyl,(halogenated C₁-C₄-alkyl)aminocarbonyl, C₆-C₁₂-arylaminocarbonyl,C₂-C₆-alkenyl, C₂-C₆-alkynyl, optionally substituted C₆-C₁₂-aryl,hydroxy, C₁-C₆-alkoxy, halogenated C₁-C₆-alkoxy, C₁-C₆-hydroxyalkoxy,C₁-C₆-alkoxy-C₁-C₄-alkoxy, amino-C₁-C₄-alkoxy,C₁-C₆-alkylamino-C₁-C₄-alkoxy, di-C₁-C₆-alkylamino-C₁-C₄-alkoxy,C₁-C₆-alkylcarbonylamino-C₁-C₄-alkoxy,C₆-C₁₂-arylcarbonylamino-C₁-C₄-alkoxy,C₁-C₆-alkoxycarbonylamino-C₁-C₄-alkoxy, C₆-C₁₂-aryl-C₁-C₄-alkoxy,C₁-C₆-alkylsulfonylamino-C₁-C₄-alkoxy, (halogenatedC₁-C₆-alkyl)sulfonylamino-C₁-C₄-alkoxy,C₆-C₁₂-arylsulfonylamino-C₁-C₄-alkoxy,(C₆-C₁₂-aryl-C₁-C₆-alkyl)sulfonylamino-C₁-C₄-alkoxy,C₃-C₁₂-heterocyclylsulfonylamino-C₁-C₄-alkoxy,C₃-C₁₂-heterocyclyl-C₁-C₄-alkoxy, C₆-C₁₂-aryloxy,C₃-C₁₂-heterocyclyloxy, C₁-C₆-alkylthio, halogenated C₁-C₆-alkylthio,C₁-C₆-alkylamino, (halogenated C₁-C₆-alkyl)amino, di-C₁-C₆-alkylamino,di-(halogenated C₁-C₆-alkyl)amino, C₁-C₆-alkylcarbonylamino,(halogenated C₁-C₆-alkyl)carbonylamino, C₆-C₁₂-arylcarbonylamino,C₁-C₆-alkylsulfonylamino, (halogenated C₁-C₆-alkyl)sulfonylamino,C₆-C₁₂-arylsulfonylamino or optionally substituted C₃-C₁₂-heterocyclyl;W is —NR⁸— or a bond; A¹ is optionally substituted C₁-C₄-alkylene or abond; Q is —S(O)₂— or —C(O)—; Y is —NR⁹— or a bond; A² is optionallysubstituted C₁-C₄-alkylene, C₁-C₄-alkylene-CO—, —CO—C₁-C₄-alkylene,C₁-C₄-alkylene-O—C₁-C₄-alkylene, C₁-C₄-alkylene-NR¹⁸—C₁-C₄-alkylene,optionally substituted C₂-C₄-alkenylen, optionally substitutedC₂-C₄-alkynylene, optionally substituted C₆-C₁₂-arylene, optionallysubstituted C₆-C₁₂-heteroarylene or a bond; X¹ is —O—, —NR¹¹—, —S—,optionally substituted C₁-C₄-alkylene, optionally substitutedC₂-C₄-alkenylen, optionally substituted C₂-C₄-alkynylene; R² ishydrogen, halogen, C₁-C₆-alkyl, halogenated C₁-C₄-alkyl,hydroxy-C₁-C₄-alkyl, —CN, C₂-C₆-alkenyl, C₂-C₆-alkynyl, optionallysubstituted C₆-C₁₂-aryl, hydroxy, C₁-C₆-alkoxy, halogenatedC₁-C₆-alkoxy, C₁-C₆-alkoxycarbonyl, C₂-C₆-alkenyloxy,C₆-C₁₂-aryl-C₁-C₄-alkoxy, C₁-C₆-alkylcarbonyloxy, C₁-C₆-alkylthio,C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, aminosulfonyl, amino,C₁-C₆-alkylamino, C₂-C₆-alkenylamino, nitro or optionally substitutedC₃-C₁₂-heterocyclyl, or two radicals R² together with the ring atoms ofA to which they are bound form a 5- or 6 membered ring; R³ is hydrogen,halogen, C₁-C₆-alkyl or C₁-C₆-alkoxy, or two radicals R³ together withthe carbon atom to which they are attached form a carbonyl group; Y¹ isoptionally substituted C₁-C₄-alkylene; R^(4a) is hydrogen, C₁-C₆-alkyl,C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl, halogenated C₁-C₄-alkyl,hydroxy-C₁-C₄-alkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl, amino-C₁-C₄-alkyl, CH₂CN,C₆-C₁₂-aryl-C₁-C₄-alkyl, C₃-C₁₂-cycloalkyl, —CHO, C₁-C₄-alkylcarbonyl,(halogenated C₁-C₄-alkyl)carbonyl, C₆-C₁₂-arylcarbonyl,C₁-C₄-alkoxycarbonyl, C₆-C₁₂-aryloxycarbonyl, C₁-C₆-alkylaminocarbonyl,C₂-C₆-alkenyl, —C(═NH)NH₂, —C(═NH)NHCN, C₁-C₆-alkylsulfonyl,C₆-C₁₂-arylsulfonyl, amino, —NO or C₃-C₁₂-heterocyclyl; or R^(4a) isoptionally substituted C₁-C₄-alkylene that is bound to a carbon atom inY¹; R^(4b) is hydrogen, C₁-C₆-alkyl, halogenated C₁-C₄-alkyl,hydroxy-C₁-C₄-alkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl, amino-C₁-C₄-alkyl, CH₂CN,—CHO, C₁-C₄-alkylcarbonyl, (halogenated C₁-C₄-alkyl)carbonyl,C₆-C₁₂-arylcarbonyl, C₁-C₄-alkoxycarbonyl, C₆-C₁₂-aryloxycarbonyl,C₁-C₆-alkylaminocarbonyl, C₂-C₆-alkenyl, —C(═NH)NH₂, —C(═NH)NHCN,C₁-C₆-alkylsulfonyl, C₆-C₁₂-arylsulfonyl, amino, —NO orC₃-C₁₂-heterocyclyl; or R^(4a), R^(4b) together are optionallysubstituted C₁-C₆-alkylene, wherein one —CH₂— of C₁-C₄-alkylene may bereplaced by an oxygen atom or —NR¹⁶; X² is —O—, —NR⁶—, —S—,>CR^(12a)R^(12b) or a bond; X³ is —O—, —NR'-, —S—, >CR^(13a)R^(13b) or abond; R⁵ is optionally substituted C₆-C₁₂-aryl, optionally substitutedC₃-C₁₂-cycloalkyl or optionally substituted C₃-C₁₂-heterocyclyl; n is 0,1 or 2; R⁶ is hydrogen or C₁-C₆-alkyl; R⁷ is hydrogen or C₁-C₆-alkyl; R⁸is hydrogen or C₁-C₆-alkyl; R⁹ is hydrogen, C₁-C₆-alkyl,C₃-C₁₂-cycloalkyl, amino-C₁-C₆-alkyl, optionally substitutedC₆-C₁₂-aryl-C₁-C₄-alkyl or C₃-C₁₂-heterocyclyl; or R⁹, R¹ together areC₁-C₄-alkylene; or R⁹ is C₁-C₄-alkylene that is bound to a carbon atomin A² and A² is C₁-C₄-alkylene or to a carbon atom in X¹ and X¹ isC₁-C₄-alkylene; R¹⁰ is hydrogen, C₁-C₆-alkyl or C₁-C₆-alkylsulfonyl; R¹¹is hydrogen or C₁-C₆-alkyl, or R⁹, R¹¹ together are C₁-C₄-alkylene,R^(12a) is hydrogen, optionally substituted C₁-C₆-alkyl,C₁-C₆-alkylamino-C₁-C₄-alkyl, di-C₁-C₆-alkylamino-C₁-C₄-alkyl,C₃-C₁₂-heterocyclyl-C₁-C₆-alkyl, optionally substituted C₆-C₁₂-aryl orhydroxy; R^(12b) is hydrogen or C₁-C₆-alkyl, or R^(12a), R^(12b)together are carbonyl or optionally substituted C₁-C₄-alkylene, whereinone —CH₂— of C₁-C₄-alkylene may be replaced by an oxygen atom or —NR¹⁴—;R^(13a) is hydrogen, optionally substituted C₁-C₆-alkyl,C₁-C₆-alkylamino-C₁-C₄-alkyl, di-C₁-C₆-alkylamino-C₁-C₄-alkyl,C₃-C₁₂-heterocyclyl-C₁-C₆-alkyl, optionally substituted C₆-C₁₂-aryl orhydroxy; R^(13b) is hydrogen or C₁-C₆-alkyl, or R^(13a), R^(13b)together are carbonyl or optionally substituted C₁-C₄-alkylene, whereinone —CH₂— of C₁-C₄-alkylene may be replaced by an oxygen atom or —NR¹⁵—;R¹⁴ is hydrogen or C₁-C₆-alkyl; R¹⁵ is hydrogen or C₁-C₆-alkyl; and R¹⁶is hydrogen or C₁-C₆-alkyl, or a physiologically tolerated salt thereof.2. Compound as claimed in claim 1, wherein A is a benzene ring or a ringselected from the group consisting of the following 5- or 6-memberedheterocyclic rings:


3. Compound as claimed in claim 1, wherein —Y-A²-X¹- comprises at least2, 3 or 4 atoms in the main chain.
 4. Compound as claimed in claim 1,wherein R¹ is C₁-C₆-alkyl, C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl,C₃-C₁₂-cycloalkyl, or optionally substituted C₃-C₁₂-heterocyclyl. 5.Compound as claimed in claim 1, wherein A¹ is a bond.
 6. Compound asclaimed in claim 1, wherein W is a bond and Y is a bond, or W is a bondand Y is —NR⁹—.
 7. Compound as claimed in claim 1, wherein X¹ is —O— andA² is C₁-C₄-alkylene, or X¹ is C₁-C₄-alkylene and A² is a bond. 8.Compound as claimed in claim 1, wherein R¹—W-A¹-Q-Y-A²-X¹- isR¹—S(O)₂—NR⁹-A²-X¹- or R¹—S(O)₂—X¹—.
 9. Compound as claimed in claim 1,having the formula

wherein R¹, W, A¹, Q, Y, A², X¹, R², R³, Y¹, R^(4a), R^(4b), X², X³, R⁵,n are as defined in claim
 1. 10. Compound as claimed in claim 1, whereinY¹ is methylene or 1,2-ethylene.
 11. Compound as claimed in claim 1,wherein R^(4a) is C₁-C₆-alkyl, C₃-C₁₂-cycloalkyl or C₃-C₁₂-heterocyclyl,or R^(4a) is C₁-C₄-alkylene that is bound to a carbon atom in Y¹. 12.Compound as claimed in claim 1, wherein R^(4b) is hydrogen orC₁-C₆-alkyl.
 13. Compound as claimed in claim 1, wherein R^(4a), R^(4b)together are optionally substituted C₁-C₆-alkylene, wherein one —CH₂— ofC₁-C₄-alkylene may be replaced by an oxygen atom.
 14. Compound asclaimed in claim 1, wherein X² is CR^(12a)R^(12b) and X³ is a bond. 15.Compound as claimed in claim 1, wherein R^(12a) is hydrogen orC₁-C₆-alkyl and R^(12b) is hydrogen or C₁-C₆-alkyl, or R^(12a), R^(12b)together are optionally substituted C₁-C₄-alkylene.
 16. Compound asclaimed in claim 1, having the formula

wherein A, R, R², R³, Y¹, R^(4a), R^(4b), X², X³, n are as defined inclaim 1; and R^(17a), R^(17b), R^(17c), R^(17d), R^(17e) independentlyare hydrogen, halogen, or halogenated C₁-C₆-alkyl.
 17. Compound asclaimed in claim 1, wherein A is a benzene ring; R is R¹—W-A¹-Q-Y-A²X¹;R¹ is C₁-C₆-alkyl, C₃-C₁₂-cycloalkyl-C₁-C₄-alkyl, C₃-C₁₂-cycloalkyl, oroptionally substituted C₃-C₁₂-heterocyclyl; W is a bond; A¹ is a bond; Qis —S(O)₂—; Y is —NR⁹ or a bond; A² is C₁-C₄-alkylene or a bond; X¹ is—O— or C₁-C₄-alkylene; R² is hydrogen or halogen; R³ is hydrogen; Y¹ isoptionally substituted C₁-C₄-alkylene; R^(4a) is hydrogen, C₁-C₆-alkyl,C₃-C₁₂-cycloalkyl or C₃-C₁₂-heterocyclyl; or R^(4a) is optionallysubstituted C₁-C₄-alkylene that is bound to a carbon atom in Y¹; R^(4b)is hydrogen; or R^(4a), R^(4b), together are C₁-C₆-alkylene, wherein one—CH₂— of C₁-C₄-alkylene may be replaced by an oxygen atom; X² isCR^(12a)R^(12b); X³ is a bond; R⁵ is optionally substituted phenyl; n is0 or 1; R⁹ is hydrogen; or R⁹ is C₁-C₄-alkylene that is bound to acarbon atom in X¹ and X¹ is C₁-C₄-alkylene; R^(12a) is hydrogen; andR^(12b) is hydrogen; or R^(12a), R^(12b) together are C₁-C₄-alkylene.18. The compound as claimed in claim 1, which is:N-[2-[3-benzyl-2-(methylaminomethypindan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide;N-[2-[3-benzyl-2-(methylaminomethypindan-5-yl]oxyethyl]cyclobutanesulfonamide;N-[2-[3-benzyl-2-(methylaminomethypindan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide;N-[[3-benzyl-2-(methylaminomethypindan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[3-benzyl-2-(methylaminomethypindan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide;N-[[3-benzyl-2-(methylaminomethypindan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide;N-[[3-benzyl-2-(methylaminomethypindan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[3-benzyl-2-(methylaminomethypindan-5-yl]ethyl]cyclobutanesulfonamide;N-[[3-benzyl-2-(methylaminomethypindan-5-yl]methyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[3-benzyl-2-(methylaminomethypindan-5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide;N-[[3-benzyl-2-(methylaminomethypindan-5-yl]methyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[3-benzyl-2-(methylaminomethypindan-5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[3-benzyl-6-fluoro-2-(methylaminomethypindan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide;N-[2-[3-benzyl-6-fluoro-2-(methylaminomethypindan-5-yl]oxyethyl]-cyclobutanesulfonamide;N-[2-[3-benzyl-6-fluoro-2-(methylaminomethypindan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[3-benzyl-6-fluoro-2-(methylaminomethypindan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide;N-[[3-benzyl-6-fluoro-2-(methylaminomethypindan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide;N-[2-[3-benzyl-6-fluoro-2-(methylaminomethypindan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide;N-[[3-benzyl-6-fluoro-2-(methylaminomethypindan-5-yl]methyl]-cyclobutanesulfonamide;N-[2-[3-benzyl-6-fluoro-2-(methylaminomethyl)indan-5-yl]ethyl]-cyclobutanesulfonamide;N-[[3-benzyl-6-fluoro-2-(methylaminomethyl)indan-5-yl]methyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[3-benzyl-6-fluoro-2-(methylaminomethyl)indan-5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide;N-[[3-benzyl-6-fluoro-2-(methylaminomethyl)indan-5-yl]methyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[3-benzyl-6-fluoro-2-(methylaminomethyl)indan-5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-indan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-indan-5-yl]oxyethyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-indan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-indan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-benzyl-indan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-indan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-benzyl-indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-indan-5-yl]ethyl]cyclobutanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-benzyl-indan-5-yl]methyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-indan-5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-benzyl-indan-5-yl]methyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-indan-5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-6-fluoro-indan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-6-fluoro-indan-5-yl]oxyethyl]-cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-6-fluoro-indan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-6-fluoro-indan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-benzyl-6-fluoro-indan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-6-fluoro-indan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-benzyl-6-fluoro-indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-6-fluoro-indan-5-yl]ethyl]cyclobutanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-benzyl-6-fluoro-indan-5-yl]methyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-6-fluoro-indan-5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-benzyl-6-fluoro-indan-5-yl]methyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-benzyl-6-fluoro-indan-5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide;1-cyclopropyl-N-[2-[3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]oxyethyl]methanesulfonamide;N-[2-[3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]oxyethyl]-cyclobutanesulfonamide;N-[2-[3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]oxyethyl]-1-methylimidazole-4-sulfonamide;N-[2-[3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]oxyethyl]-1-methylpyrazole-4-sulfonamide;1-cyclopropyl-N-[[3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]methyl]methanesulfonamide;1-cyclopropyl-N-[2-[3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]ethyl]methanesulfonamide;N-[2-[3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]methyl]-cyclobutanesulfonamide;N-[2-[3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]ethyl]cyclobutanesulfonamide;N-[[3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]methyl]-1-methylimidazole-4-sulfonamide;N-[2-[3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]ethyl]-1-methylimidazole-4-sulfonamide;N-[[3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]methyl]-1-methylpyrazole-4-sulfonamide;N-[2-[3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]ethyl]-1-methylpyrazole-4-sulfonamide;1-cyclopropyl-N-[2-[6-fluoro-3-[(3-fluorophenyl)methyl]-2-(methylaminomethypindan-5-yl]oxyethyl]methanesulfonamide;N-[2-[6-fluoro-3-[(3-fluorophenyl)methyl]-2-(methylaminomethypindan-5-yl]oxyethyl]cyclobutanesulfonamide;N-[2-[6-fluoro-3-[(3-fluorophenyl)methyl]-2-(methylaminomethypindan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[6-fluoro-3-[(3-fluorophenyl)methyl]-2-(methylaminomethypindan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide;1-cyclopropyl-N-[[6-fluoro-3-[(3-fluorophenyl)methyl]-2-(methylaminomethypindan-5-yl]methyl]methanesulfonamide;1-cyclopropyl-N-[2-[6-fluoro-3-[(3-fluorophenyl)methyl]-2-(methylaminomethypindan-5-yl]ethyl]methanesulfonamide;N-[[6-fluoro-3-[(3-fluorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[6-fluoro-3-[(3-fluorophenyl)methyl]-2-(methylaminomethypindan-5-yl]ethyl]cyclobutanesulfonamide;N-[[6-fluoro-3-[(3-fluorophenyl)methyl]-2-(methylaminomethypindan-5-yl]methyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[6-fluoro-3-[(3-fluorophenyl)methyl]-2-(methylaminomethypindan-5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide;N-[[6-fluoro-3-[(3-fluorophenyl)methyl]-2-(methylaminomethypindan-5-yl]methyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[6-fluoro-3-[(3-fluorophenyl)methyl]-2-(methylaminomethypindan-5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-fluorophenyl)methyl]indan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-fluorophenyl)methyl]indan-5-yl]oxyethyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-fluorophenyl)methyl]indan-5-yl]oxyethyl]-1-methylimidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-fluorophenyl)methyl]indan-5-yl]oxyethyl]-1-methylpyrazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[(3-fluorophenyl)methyl]indan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-fluorophenyl)methyl]indan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[(3-fluorophenyl)methyl]indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-fluorophenyl)methyl]indan-5-yl]ethyl]cyclobutanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[(3-fluorophenyl)methyl]indan-5-yl]methyl]-1-methylimidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-fluorophenyl)methyl]indan-5-yl]ethyl]-1-methylimidazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[(3-fluorophenyl)methyl]indan-5-yl]methyl]-1-methylpyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-fluorophenyl)methyl]indan-5-yl]ethyl]-1-methylpyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]oxyethyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]ethyl]cyclobutanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]methyl]-1-methylimidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]ethyl]-1-methylimidazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]methyl]-1-methylpyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[(3-fluorophenyl)methyl]indan-5-yl]ethyl]-1-methylpyrazole-4-sulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]oxyethyl]cyclobutanesulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]oxyethyl]-1-methylimidazole-4-sulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]oxyethyl]-1-methylpyrazole-4-sulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]oxyethyl]-1-methylpyrazole-4-sulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide;N-[[3-[(3-chlorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]ethyl]cyclobutanesulfonamide;N-[[3-[(3-chlorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]methyl]-1-methylimidazole-4-sulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]ethyl]-1-methylimidazole-4-sulfonamide;N-[[3-[(3-chlorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]methyl]-1-methylpyrazole-4-sulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-2-(methylaminomethyl)indan-5-yl]ethyl]-1-methylpyrazole-4-sulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-6-fluoro-2-(methylaminomethyl)indan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-6-fluoro-2-(methylaminomethyl)indan-5-yl]oxyethyl]cyclobutanesulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-6-fluoro-2-(methylaminomethyl)indan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-6-fluoro-2-(methylaminomethyl)indan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide;N-[[3-[(3-chlorophenyl)methyl]-6-fluoro-2-(methylaminomethyl)indan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-6-fluoro-2-(methylaminomethyl)indan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide;N-[[3-[(3-chlorophenyl)methyl]-6-fluoro-2-(methylaminomethyl)indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-6-fluoro-2-(methylaminomethyl)indan-5-yl]ethyl]cyclobutanesulfonamide;N-[[3-[(3-chlorophenyl)methyl]-6-fluoro-2-(methylaminomethyl)indan-5-yl]methyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-6-fluoro-2-(methylaminomethyl)indan-5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide;N-[[3-[(3-chlorophenyl)methyl]-6-fluoro-2-(methylaminomethyl)indan-5-yl]methyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[3-[(3-chlorophenyl)methyl]-6-fluoro-2-(methylaminomethyl)indan-5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]indan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]indan-5-yl]oxyethyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]indan-5-yl]oxyethyl]-1-methylimidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]indan-5-yl]oxyethyl]-1-methylpyrazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]indan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]indan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]indan-5-yl]ethyl]cyclobutanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]indan-5-yl]methyl]-1-methylimidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]indan-5-yl]ethyl]-1-methylimidazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]indan-5-yl]methyl]-1-methylpyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]indan-5-yl]ethyl]-1-methylpyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]oxyethyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]ethyl]cyclobutanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]methyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]methyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[(3-chlorophenyl)methyl]-6-fluoro-indan-5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide;1-cyclopropyl-N-[2-[2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]methanesulfonamide;N-[2-[2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]cyclobutanesulfonamide;1-methyl-N-[2-[2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]imidazole-4-sulfonamide;1-methyl-N-[2-[2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]pyrazole-4-sulfonamide;1-cyclopropyl-N-[[2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]methanesulfonamide;1-cyclopropyl-N-[2-[2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]methanesulfonamide;N-[[2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]cyclobutanesulfonamide;1-methyl-N-[[2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]imidazole-4-sulfonamide;1-methyl-N-[2-[2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]imidazole-4-sulfonamide;1-methyl-N-[[2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]pyrazole-4-sulfonamide;1-methyl-N-[2-[2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]pyrazole-4-sulfonamide;1-cyclopropyl-N-[[6-fluoro-2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]methanesulfonamide;N-[2-[6-fluoro-2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]cyclobutanesulfonamide;N-[2-[6-fluoro-2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[6-fluoro-2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide;1-cyclopropyl-N-[[6-fluoro-2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]methanesulfonamide;1-cyclopropyl-N-[2-[6-fluoro-2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]methanesulfonamide;N-[[6-fluoro-2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[6-fluoro-2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]cyclobutanesulfonamide;N-[[6-fluoro-2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[6-fluoro-2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide;N-[[6-fluoro-2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[6-fluoro-2-(methylaminomethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]cyclobutanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]oxyethyl]-1-methyl-pyrazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]-1-cyclopropyl-methanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]-1-cyclopropyl-methanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]cyclobutanesulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]cyclobutanesulfonamide;N-[[2-(azetidin-1-ylmethyl)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]-1-methyl-imidazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]-1-methyl-imidazole-4-sulfonamide;N-[[2-(azetidin-1-ylmethyl)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]methyl]-1-methyl-pyrazole-4-sulfonamide;N-[2-[2-(azetidin-1-ylmethyl)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methyl]indan-5-yl]ethyl]-1-methyl-pyrazole-4-sulfonamide;or a physiologically tolerated salt thereof.
 19. Pharmaceuticalcomposition which comprises a carrier and a compound of claim
 1. 20. Amethod for treating a neurologic or psychiatric disorder or pain in amammalian patient in need thereof which comprises administering to thepatient a therapeutically effective amount of a compound of claim 1.